PReD-Bench/PRed-Bench huggingface dataset:
Dasatinib enhances cisplatin sensitivity in human esophageal squamous cell carcinoma (ESCC) cells via suppression of PI3K/AKT and Stat3 pathways
Authors: Nan Kang
Tian Lan
Weimin Zhang
Kangtai Liu
Ming Fu
Lijia Dong
Cuixiang Zhang
Bing Liu
Qimin Zhan
Jincai Hou
Jie Chen
Journal: Archives of Biochemistry and Biophysics (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AKT; Cisplatin; Dasatinib; ESCC; Stat3.
Affiliations: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100191, China., State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100191, China; Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100191, China., Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China., National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University and Chinese Academy of MedicalSciences, Beijing 100005, China., Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 110300, China., State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100191, China. Electronic address: .

Abstract:  The clinical efficacy of cisplatin in esophageal squamous cell carcinoma (ESCC) treatment remains undesirable. Src, a non-receptor tyrosine kinase involved in multiple fields of tumorigenesis, recently has been indicated as a promising therapeutic target in the treatment of solid tumors including ESCC. However, whether inhibition of Src activity can increase cisplatin efficacy in ESCC cells remains unknown. The present study found that inhibition of Src by its inhibitor-dasatinib sensitized ESCC cells to cisplatin in vitro. Our data also suggest a likely mechanism for this synergy that dasatinib reduces expression of critical oncogenic members of the signaling pathways, such as AKT or Stat3, and cisplatin-resistant molecules, such as ERCC1 and BRCA1, under the control of Src. Furthermore, dasatinib could sensitize ESCC cells to another platin-based agent, carboplatin. Therefore, this study provides a potential target for improving cisplatin efficacy in ESCC therapy. 

Retracted: No

PubPeer comments:
 Figure 1E appears to include a repeated image. *** ![file] ,
Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia
Authors: Nicholas C Wolff
James Brugarolas
Xian-Jin Xie
Diego H Castrillon
Silvia Vega-Rubin-de-Celis
Wareef Kabbani
Journal: Molecular and Cellular Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTORC1; hypoxia; Redd1; Tsc1/Tsc2; liver
Affiliations: University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9133, USA.

Abstract:  mTORC1 is a critical regulator of cell growth that integrates multiple signals and is deregulated in cancer. We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex. Here we show that Redd1 induction by hypoxia is tissue dependent and that hypoxia signals are relayed to mTORC1 through different pathways in a tissue-specific manner. In the liver, Redd1 induction is restricted to the centrilobular area, and in primary hepatocytes, mTORC1 inhibition by hypoxia is independent of Redd1. Furthermore, Tsc1/Tsc2 and Arnt (Hif-1β) are similarly dispensable. Hypoxia signaling in hepatocytes involves Lkb1, AMP-activated protein kinase (AMPK), and raptor. Differences in signal relay extend beyond hypoxia and involve AMPK signaling. AMPK activation (using 5-aminoimidazole-4-carboxamide riboside [AICAR]) induces raptor phosphorylation and inhibits mTORC1 in both mouse embryo fibroblasts (MEFs) and hepatocytes, but whereas mTORC1 inhibition is Tsc1/Tsc2 dependent in MEFs, it is independent in hepatocytes. In liver cells, raptor phosphorylation is essential for both AMPK and hypoxia signaling. Thus, context-specific signals are required for raptor phosphorylation-induced mTORC1 inhibition. Our data illustrate a heretofore unappreciated topological complexity in mTORC1 regulation. Interestingly, topological differences in mTORC1 regulation by the tumor suppressor proteins Lkb1 and Tsc1/Tsc2 may underlie their tissue specificity of tumor suppressor action. 

Retracted: No

PubPeer comments:
 2017 correction. http: mcb.asm.org content 37 13 e00224-17.full , 
 The correction reads:  *Fig. 2A, row 3: The second image is incorrect. The corrected image should appear as shown below. We regret the error. This change does not affect the interpretation of the data and conclusions of the study.* Here is Figure 2A as reported to the journal in October 2016. The image is made darker to bring out details. Red boxes draw attention to possible overlapping areas. Now that I look at this image again, I find the enlarged images below (Liver 0 and 1) also very similar to each other, and I have marked those with yellow boxes. The yellow boxes were not part of my report to the journal in 2016. Only the duplication marked in red has been addressed in the Correction. Could the authors please take another look? ![file] This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
Upregulation of histamine receptor H1 promotes tumor progression and contributes to poor prognosis in hepatocellular carcinoma
Authors: Jibin Li
Tian Gao
Chun Yin
Yiran Hou
Jiaze An
Xiaojun Huang
Jing Zhao
Jinliang Xing
Xiaohong Zhang
Shaogui Wan
Jing Hu
Journal: Oncogene (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: H1 histamine receptor; hepatocellular carcinoma; tumor progression; cancer; cell cycle progression
Affiliations: Center for Molecular Pathology, First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, 341000, China., State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Medical College of Yan'an University, Yan'an, Shaanxi, 716000, China., Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China., Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China., Center for Molecular Pathology, First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. ., State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. .

Abstract:  H1 histamine receptor (H1HR) belongs to the family of rhodopsin-like G-protein-coupled receptors. Recent studies have shown that H1HR expression is increased in several types of cancer. However, its functional roles in tumor progression remain largely unknown, especially in hepatocellular carcinoma (HCC). We found that H1HR is frequently unregulated in HCC, which is significantly associated with both recurrence-free survival and overall survival in HCC patients. Functional experiments revealed that H1HR promoted both the growth and metastasis of HCC cells by inducing cell cycle progression, formation of lamellipodia, production of matrix metalloproteinase 2, and suppression of cell apoptosis. Activation of cyclic adenosine monophosphate-dependent protein kinase A was found to be involved in H1HR-mediated HCC cell growth and metastasis. In addition, we found that overexpression of H1HR was mainly due to the downregulation of miR-940 in HCC cells. Moreover, the H1HR inhibitor terfenadine significantly suppressed tumor growth and metastasis in an HCC xenograft nude mice model. Our findings demonstrate that H1HR plays a critical role in the growth and metastasis of HCC cells, which provides experimental evidence supporting H1HR as a potential drug target for the treatment of HCC. 

Retracted: No

PubPeer comments:
 Figure 4B and Figure 6G appear to have a duplicated image, although the coloring appears to have been altered, suggesting that this was not simply an error during figure assembly. *** ![file] , 
 Another set of repeated recolored images in 4B and Figure 6G. I am not sure the results presented in this paper are reliable. *** ![file] , 
 Although not critical, there seems to also be a duplicated image within Figure 6F. *** ![file] , 
 Another possible issue within Figure 6F. ![file] ,
Nucleolar localization of the Notch4 intracellular domain underpins its regulation of the cellular response to genotoxic stressors
Authors: Apurva Sarin
Neetu Saini
Journal: Cell Death Discovery (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Apoptosis; Breast cancer.
Affiliations: Institute for Stem Cell Science & Regenerative Medicine (inStem), Bellary Road, Bengaluru, Karnataka India., 2Department of Biology, Manipal Academy of Higher Education, Manipal, India.

Abstract:  Cell survival is one of the many cellular processes regulated by Notch family of proteins. A comparison of human breast cancer cell lines, which differ in the levels of endogenous Notch4, implicated the protein in regulating susceptibility to apoptosis triggered by genomic damage. In agreement with this observation, increased susceptibility to genotoxic damage was observed following siRNA ablations of Notch4 in two breast cancer cell lines. Further, overexpressing Notch4 intracellular domain (NIC4) tagged to GFP (NIC4-GFP), protected cells from apoptosis triggered by genotoxic drugs. In cells immune-stained for endogenous Notch4, protein was detected in the nucleolus and nucleoplasm, which was also confirmed by the co-localization of NIC4-GFP with RFP-tagged nucleolar proteins in breast cancer cells or the unrelated HEK cell line. Linking functional outcomes to nucleolar localization, NIC4-GFP protection from apoptosis, required the nucleolar proteins Nucleolin and Fibrillarin. Consistently, immunoprecipitation analysis revealed associations between nucleolar proteins-Nucleolin and Nucleophosmin-and Notch4. Microscopy-based biophysical analysis of live cells showed that nucleolar and nucleoplasmic pools of NIC4-GFP are mobile, with some sequestration of nucleolar NIC4-GFP pools. A nucleolar excluded form, NIC4_3RA-GFP, generated by site-directed mutagenesis of the nucleolar localization sequence in NIC4, could not protect from apoptosis triggered by genotoxic stressors. However, transcriptional activity or protection from apoptosis triggered by endoplasmic stress was comparable in cells expressing NIC4_3RA-GFP or NIC4-GFP. Together, the data show that nucleolar localization of NIC4 is critical for the regulation of genomic damage and may be uncoupled from its activities in the nucleoplasm. This study identifies intrinsic features of NIC4 that regulate signaling outcomes activated by the receptor by controlling its spatial localization. 

Retracted: No

PubPeer comments:
 On page 3, the exercise score (e.g., TRIMP) for each bout was computed by multiplying the duration of the exercise bout by the session RPE for that bout. Afterwards, IN THE SAME PARAGRAPH, the same exercise score (i.e., TRIMP) calculus was presented differently. ![file] ,
Fission yeast Mcm10p contains primase activity
Authors: Karen Fien
Jerard Hurwitz
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mcm10p; primase activity; RNA primers; DNA polymerases; Schizosaccharomyces pombe
Affiliations: Program of Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. 

Abstract:  Although Mcm10p is a conserved essential component in eukaryotes required for both the initiation and elongation of DNA chains, its biochemical properties are unknown. Here, we report that the Schizosaccharomyces pombe fission yeast Mcm10 protein contains primase activity. Primases are enzymes that synthesize RNA primers on single-stranded DNA templates that are extended by DNA polymerases. In keeping with this property, Mcm10p supported oligoribonucleotide synthesis of short RNA primers (preferentially initiating synthesis on a dT template) that were extended with dATP by Escherichia coli DNA polymerase I. The C terminus of Mcm10p synthesized RNA, but less efficiently than the full-length protein at low rNTP levels. Mcm10p homologs contain a C-terminal motif found in proteins that polymerize nucleotides. A point mutant within this motif of S. pombe Mcm10p was defective in primer synthesis in vitro, and this mutant failed to support growth in vivo, suggesting that the primase activity of Mcm10p may be essential for cell viability. 

Retracted: No

PubPeer comments:
 ![file] Thereu2019s an undeclared splicing site in Figure 3A. It seems that no sample was loaded in the last lane of I-303 panel. ,
dSet1 is the main H3K4 di- and tri-methyltransferase throughout Drosophila development
Authors: Kathleen A Fitzpatrick
Graham Hallson
Inho Kim
Donald A R Sinclair
Shawn Cotsworth
Monika Syrzycka
Barry M Honda
Taosui Li
Robert E Hollebakken
Journal: Genetics (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: eukaryotes; post-translational; methyl groups; histone H3 lysine 4; gene expression patterns
Affiliations: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.

Abstract:  In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a "global" or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di- and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans. 

Retracted: No

PubPeer comments:
 Figure 1A of Hallson et al., 2012 and Supplemental Fig. S1 of Hallson et al., 2008 used very similar images (which might implicate image duplication), although the Drosophila strains and genes analyzed differ. Could authors provide an explanation, please? ![file] ,
Phytochemical evaluation and anticancer activity of rambutan (Nephelium lappaceum) fruit endocarp extracts against human hepatocellular carcinoma (HepG-2) cells
Authors: Sandhanasamy Devanesan
Mohamad S AlSalhi
Rajesh Selvaraj
Angalammal Perumal
Sivakumari Kanakarajan
Vairakannu Tamizhazhagan
Journal: Saudi Journal of Biological Sciences (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ATR and GC–MS; Anticancer; Apoptotic study; Nephelium lappaceum; Phytochemicals.
Affiliations: Department of Zoology, Presidency College, Chennai 600005, India., Department of Physics and Astronomy, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia., Department of Zoology, Syed Ammal Arts and Science College, Ramanathapuram 623513, India.

Abstract:  The current investigation was taken to screen the phytoconstituents present in fruit endocarp various extracts of Nephelium lappaceum commonly called as Rambutan fruit and its anticancer property against human hepatocellular carcinoma (HepG-2) cells. Different analytical techniques including qualitative phytochemical analysis, cell viability assay (MTT), apoptotic nuclear staining (DAPI), DNA fragmentation assay, Attenuated total reflection (ATR) and Gas chromatography-mass spectrometry (GC-MS) spectral analysis were carried out. ATR and GC-MS study revealed the presence of functional groups and 9 compounds, respectively in methanol endocarp extract. The results obtained depicts that methanol endocarp extract profoundly controlled cell proliferation and caused shrinkage of HepG-2 cells from polygonal to spherical shape. DAPI staining revealed that methanol endocarp extract caused increased fragmentation of nucleus and DNA fragmentation, which can be taken as a sign of apoptosis. The anticancer potential of methanol fruit endocarp extract of Nephelium lappaceum than other extracts and could be used successfully in future drug delivery systems and other biomedical concerns. 

Retracted: No

PubPeer comments:
 A number of images in Figure 4 appear to overlap. Annotated here by ImageTwin. *** ![file] , 
 Figure 6: Some bands from the ladder have been copied into a sample lane, I ve added the red boxes to show where I mean. Would the authors please comment? ![file] , 
 Having reviewed my above comment I think the copy and paste issue is clearer without the boxes obscuring the edges, so I have included Figure 6, without boxes, below. ![file] ,
The set1Delta mutation unveils a novel signaling pathway relayed by the Rad53-dependent hyperphosphorylation of replication protein A that leads to transcriptional activation of repair genes
Authors: Vera Schramke
Holger Neecke
Vanessa Brevet
Yves Corda
Giovanna Lucchini
Maria Pia Longhese
Eric Gilson
Vincent Géli
Journal: Genes & Development (2001)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SET domain proteins; epigenetic control; transcription; yeast; Set1p

Abstract: SET domain proteins are present in chromosomal proteins involved in epigenetic control of transcription. The yeast SET domain protein Set1p regulates chromatin structure, DNA repair, and telomeric functions. We investigated the mechanism by which the absence of Set1p increases DNA repair capacities of checkpoint mutants. We show that deletion ofSET1 induces a response relayed by the signaling kinase Rad53p that leads to the MEC1/TEL1-independent hyperphosphorylation of replication protein A middle subunit (Rfa2p). Consequently, the binding of Rfa2p to upstream repressing sequences (URS) of repair genes is decreased, thereby leading to their derepression. Our results correlate the set1Δ-dependent phosphorylation of Rfa2p with the transcriptional induction of repair genes. Moreover, we show that the deletion of the amino-terminal region of Rfa2p suppresses the sensitivity to ultraviolet radiation of amec3Δ checkpoint mutant, abolishes the URS-mediated repression, and increases the expression of repair genes. This work provides an additional link for the role of Rfa2p in the regulation of the repair capacity of the cell and reveals a role for the phosphorylation of Rfa2p and unveils unsuspected connections between chromatin, signaling pathways, telomeres, and DNA repair. 

Retracted: No

PubPeer comments:
null, 
null, 
 #1 Fresh illustration of figure 2A. Much more similar than you would expect. https: imgur.com cqqpphFu00a0u00a0 New observation on figures 2A and 2B. Much more similar than you would expect. https: imgur.com wqEkwTY ,
CHK1 affects cell sensitivity to microtubule-targeted drugs
Authors: Ya Wang
Adam Dicker
Qing Ren
Ronghua Liu
Journal: Journal of cellular physiology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Microtubules; Anticancer drugs; Drug resistance; Tumor control; CHK1
Affiliations: Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Abstract:  Microtubules are the target of many anticancer drugs. Understanding the mechanism by which cells respond to different microtubule-targeted drugs is important to resolve the drug resistance and to gain better tumor control. We report here for the first time that CHK1, an essential protein in mammalian cells, affects cell sensitivity to microtubule-targeted drugs. By using a pair of transformed rat fibroblast cell lines, we show that compared with their counterpart B4 cells, A1-5 cells with higher CHK1 expression are more resistant to taxotere, a microtubule stabilizer, but are more sensitive to nocodazole, a microtubule destabilizer. We also show that the altered sensitivities of A1-5 cells to either taxotere or to nocodazole are related to the lesser microtubule-formation in the cells. In addition, we show that the altered drug sensitivities and less microtubules-formation shown in A1-5 cells could be efficiently reversed by Chk1 siRNA. Taken together, these results indicate that CHK1 is one of the factors affecting cell resistance to taxotere and sensitiveness to nocodazole, suggesting that CHK1 is involved in affecting microtubule dynamics and could be inhibited for taxotere sensitization in CHK1 highly expressed tumor cells. 

Retracted: No

PubPeer comments:
 Figure 4A. Total tubulin panel. Much more similar than you would expect. https: imgur.com zRzwuuy , 
 #1 Much more similar that you would expect. https: imgur.com vvwdLMq , 
 Figures 2A and 4A. Much more similar and different than you would expect. https: imgur.com TvA61cT ,
In vitro and in vivo biocompatibility study of polyacrylate TiO2@Ag coated nanoparticles for the radiation dose enhancement
Authors: Sadia Bano
Ateeque Ur Rehman
Muhammad Naeem Anjum
Khizir Farooq
Muhammad Hassan
Aun Raza
Journal: Artificial Cells Nanomedicine and Biotechnology (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Silver; biocompatible nanoparticles; macrophage cells; polymer gel; radiation therapy
Affiliations: Medical Physics Group, Department of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan., School of Pharmacy, The University of Queensland Brisbane, Brisbane, Australia., Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.

Abstract:  To enhance the efficacy of radiation therapy, functionalised core-shell nanoparticles (CS NPs) are used as a radiosensitizer. These NPs can act as a therapeutic agent and carrier for other therapeutic agents. In this study, the first poly-acrylic acid modified silver-coated titanium dioxide NPs were fabricated to evaluate the radiation dose enhancement within the human tissue equivalent polymer gel after investigating the biocompatibility. Macrophage cell line and rats model were used for in vitro and in vivo study respectively. Two different beam qualities were applied to quantify the radiation dose enhancement with different concentrations of NPs in the polymer gel. The dose enhancement factors (DEFs) indicated that these biocompatible CS NPs are more effective for the radiation dose enhancement at low energy x-rays (80 kV) as compared to the high energy gamma (1.25 MeV Co60). These results suggested that functionalised core-shell silver-coated titanium dioxide NPs have great potential as a radiosensitizer in radiation therapy. 

Retracted: Yes

PubPeer comments:
 The manipulation of the microscopy data in Figure 7 is enough to forget this paper. ![file] , 
 **Retracted** February 3, 2023 u201cWe, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Ateeque Ur Rehman, Muhammad Hassan, Sadia Bano, Khizir Farooq, Aun Raza Muhammad Naeem Anjum (2021) In vitro and in vivo biocompatibility study of polyacrylate TiO2@Ag coated nanoparticles for the radiation dose enhancement. Artificial Cells, Nanomedicine, and Biotechnology, 49(1), 185u2013193, DOI: 10.1080 21691401.2021.1889574 Since publication, concerns were raised about the methods and some images in this article. Specifically, some images in Figure 7 have been duplicated and rotated. When approached for an explanation, the authors were unable to provide a satisfactory explanation for this. The corresponding author has been informed of our decision to retract. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. u201c ,
EGFR/ARF6 regulation of Hh signalling stimulates oncogenic Ras tumour overgrowth
Authors: Da-Ming Li
Tian Xu
Chiswili Chabu
Journal: Nature Communications (2017)
Discipline: Multidisciplinary
Keywords: Oncogenic Ras; Egfr; Hedgehog signalling; Arf6; Drosophila tumour model

Abstract:  Multiple signalling events interact in cancer cells. Oncogenic Ras cooperates with Egfr, which cannot be explained by the canonical signalling paradigm. In turn, Egfr cooperates with Hedgehog signalling. How oncogenic Ras elicits and integrates Egfr and Hedgehog signals to drive overgrowth remains unclear. Using a Drosophila tumour model, we show that Egfr cooperates with oncogenic Ras via Arf6, which functions as a novel regulator of Hh signalling. Oncogenic Ras induces the expression of Egfr ligands. Egfr then signals through Arf6, which regulates Hh transport to promote Hh signalling. Blocking any step of this signalling cascade inhibits Hh signalling and correspondingly suppresses the growth of both, fly and human cancer cells harbouring oncogenic Ras mutations. These findings highlight a non-canonical Egfr signalling mechanism, centered on Arf6 as a novel regulator of Hh signalling. This explains both, the puzzling requirement of Egfr in oncogenic Ras-mediated overgrowth and the cooperation between Egfr and Hedgehog. 

Retracted: No

PubPeer comments:
 The problems in Figure 3 and Figure 7 C and E have been corrected (please see published erratum). The last issue has not been corrected. ![file] ![file] ![file] , 
 #1 I believe that there is a problem in 7H as well. ![file] 7I not looking so good either. ![file] 7J: ![file] , 
 #2 7G too. I ll leave the other panels of Fig 7 for other commenters. ![file] , 
 Not entirely trusting Fig 7M. ![file] , 
 #2 7J again. I keep seeing more. ![file] Update: the resolution of images is much better on the PDF version of the paper , and it allows one to appreciate the amount of work that went into them, at the level of individual cells as well as groups of cells. ![file] , 
 #3 Can I have a do-over on Fig 7F? ![file] , 
 Unbelievable! The chinese open up a hole new world where everything is possible! NIH and US National Library of Medicine should stop using federal funds on indexing journals that publish junk science. , 
 All the panels of Fig 7 reward close attention. Their turbulence reminds me of late-career Turner paintings. ![] , 
 7B: ![file] Redoing 7H: ![file] Redoing 7I: ![file] 7M, re-annotated: ![file] , 
 #9 Extensive though well-disguised overlaps between 7L [above] and 7M [below]. ![file] Reworking (as the artists call it) in 7K. ![file] ,
Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis
Authors: Kevin W Williams
Joel K Elmquist
Yong Xu
Jong-Woo Sohn
Charlotte E Lee
Mi Hwa Kim
Chen Liu
Tiemin Liu
Eric D Berglund
Claudia R Vianna
Journal: Journal of Clinical Investigation (2013)
Discipline: CLINICAL MEDICINE
Keywords: Energy homeostasis; Glucose homeostasis; Serotonin 2C receptors; Obesity; Pro-opiomelanocortin neurons

Abstract:  Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control. 

Retracted: No

PubPeer comments:
 weird repeated data points: ![file] , 
 There are patterns in other datasets that appear to be more similar than expected. ![file] ![file] , 
 #2 Wouldn t one expect VO2 and VCO2 to be strongly correlated with a subject, both via metabolic rate and via lung capacity? ,
JQ-1 Inhibits Colon Cancer Proliferation via Suppressing Wnt/β-Catenin Signaling and miR-21
Authors: Yan Zhang
Chang Liu
Jidong Xiong
Hongyu Song
Suli Tian
Yongxu Zhou
Journal: Chemical research in toxicology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bromodomain; extraterminal; BET protein inhibitors; JQ-1; colon cancer therapy
Affiliations: Department of General Surgery , The Fourth Hospital Affiliated To Harbin Medical University , No. 37 Yiyuan Road , Harbin 150001 , China.

Abstract:  Bromodoamin and extraterminal (BET) protein inhibitors are a novel class of cancer therapeutics. Here we aim to investigate the efficacy and mechanism of JQ-1, a potent BET inhibitor, in colon cancer therapy. JQ-1 was used to treat SW480 colon cancer mouse xenografts. The tumor size and mouse survival were recorded. Cell apoptosis was evaluated by Annex V-FIC/PI flow cytometry. ChIP-q-PCR analysis was used to assess the H3K27 trimethylation (H3K27m3) of the p16 promoter. Wnt signaling was evaluated by Nkd2 and β-catenin levels. RT-PCR was used to evaluate the level of miR-21. MiR-21 was overexpressed with a lentiviral system and was used to evaluate the relationship between miR-21 and JQ-1. JQ-1 significantly reduced tumor growth, improved mouse survival, and induced apoptosis. JQ-1 epigenetically inhibited the H3K27me3 promoter activity, promoting p16 expression. Nkd2 and β-catenin were upregulated and downregulated by JQ-1, respectively. MiR-21 was downregulated by JQ-1. MiR-21 overexpression compensated for proliferation inhibition by JQ-1. Nkd2 levels were also downregulated by miR-21 overexpression. JQ-1 is effective in inhibiting colon cancer. We revealed that the mechanism of JQ-1 action is associated with its regulation of Wnt/β-catenin signaling and miR-21 levels. 

Retracted: No

PubPeer comments:
 Methods indicate  The treatment was performed 1 week after tumor inoculation using 50 mg kg JQ-1 (0.033% DMSO in PBS) or equivalent volumes of DMSO solution (0.033% in PBS) **intravenously.** i) at such dilution with so few DMSO, JQ-1 is not soluble and crystals impair IV administration. None of the previous papers used JQ-1 intravenously, in this concentration. Therefore I suspect an error with an **intraperitoneally** administration. ii) It is not indicated if it is daily administration (as usual) or single administration. I would like to know the answer from the authors. Thank you ,
<i>Retracted</i> : MicroRNA‐4429 restrains colorectal cancer cell invasion and migration via regulating SMAD3‐induced epithelial–mesenchymal transition
Authors: Yifang Shui
Hongwen Li
Weijie Liang
Zhe Zhang
Hongyu Zhang
Journal: Journal of Cellular Physiology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CRC; FOXM1; SMAD3; miR-4429.
Affiliations: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Abstract:  Colorectal cancer (CRC) is one of the commonest human cancers and the fourth primary cause of cancer-related death. Previous studies have reported that miR-4429 develops anticancer function in follicular thyroid carcinoma and non-small cell lung cancer. However, whether miR-4429 is implicated in the CRC progression remains to be clarified. The aim of our current study was to explore the potential role of miR-4429 in CRC. According to the result of quantitative real-time polymerase chain reaction analysis, miR-4429 was expressed at a low level in CRC cells. Gain-of-function assays showed that the upregulation of miR-4429 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in CRC, whereas miR-4429 inhibition led to the opposite results. It was uncovered from mechanism experiments that miR-4429 targeted forkhead box M1 (FOXM1) and therefore regulating SMAD family member 3 (SMAD3) expression. Rescue experiments elucidated that miR-4429 influenced cell proliferation, migration, invasion, and EMT process in CRC by targeting FOXM1 to inactivate SMAD3. In conclusion, our study revealed that miR-4429 targeted FOXM1 to decrease SMAD3 expression and thus impeding cell proliferation, migration, invasion, and EMT process of CRC cells. 

Retracted: Yes

PubPeer comments:
 Retracted [8 March 2022] . ---------------------------------- The above article, published online on 3 March 2021 in Wiley Online Library has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. Thus, the conclusions are considered to be invalid. ,
Overexpression of SHP2 tyrosine phosphatase promotes the tumorigenesis of breast carcinoma
Authors: Haoshu Fang
Danlei Chen
Zhongqian Hu
Siying Wang
Xinyi Wang
Zhuo Chen
Journal: Oncology Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: SHP2; breast cancer; cell proliferation; invasion; migration
Affiliations: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Abstract:  Expression of Src homology phosphotyrosine phosphatase 2 (SHP2) has been observed in human breast cancer. SHP2 is known to promote cell migration and invasiveness. However, the pathophysiologic role of SHP2 and its relevance to tumorigenesis are still largely unknown. In the present study, we aimed to evaluate the effect of SHP2 on the malignant phenotype of human breast cancer. An SHP2-overexpressing human breast cancer cell line was established by stable transfection of the SHP2 vector. The expression of SHP2 protein was detected using western blotting. The effects of SHP2 overexpression on cell proliferation were examined by an MTS assay. Invasion and migration abilities of the SHP2-overexpressing cells were determined using a Matrigel-based Boyden chamber invasion assay and a monolayer wound-healing assay. Increased SHP2 expression was detected following SHP2-vector transfection in the MDA-MB-231 cells. Overexpression of SHP2 was associated with increased cell proliferation and clone formation, and decreased chemotherapeutic sensitivity. Furthermore, transfection of SHP2 into breast cancer cells significantly promoted tumor growth in a mouse xenograft model. The mechanism of the promotion of tumorigenesis by SHP2 appears to involve its ability to increase the activity of ERK/AKT-mediated signaling pathways. In conclusion, our data suggest an important role of SHP2 in the molecular etiology of tumor growth, and implicate the potential application of SHP2 in cancer therapy. 

Retracted: No

PubPeer comments:
null, 
 #1 Agree with #1 s finding for Fig. 3B (green boxes), plus new finding in Fig. 3A (red boxes) ![file] , 
 #1 Agree with #1 s finding for Fig. 7C. Made it a demo in green boxes so easier for readers. ![file] , 
 As the above concerns have all been addressed by a corrigendum published by the authors , there is an additional issue in Fig. 4C. Fig. 4C. Looks like a reuse of the same image with scaling and cropping. ![file] ,
Induction of caveolin-3/eNOS complex by nitroxyl (HNO) ameliorates diabetic cardiomyopathy
Authors: Zhi-Yuan Wu
Jin-Song Bian
Hai-Jian Sun
Meng-Yuan Zhu
Si-Ping Xiong
Philip K Moore
Lei Cao
Journal: Redox Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; Cardiomyocytes; Diabetes; Nitroxyl; Oxidative stress.
Affiliations: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore., Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore; National University of Singapore (Suzhou) Research Institute, Suzhou, China. Electronic address: .

Abstract:  Nitroxyl (HNO), one-electron reduced and protonated sibling of nitric oxide (NO), is a potential regulator of cardiovascular functions. It produces positive inotropic, lusitropic, myocardial anti-hypertrophic and vasodilator properties. Despite of these favorable actions, the significance and the possible mechanisms of HNO in diabetic hearts have yet to be fully elucidated. H9c2 cells or primary neonatal mouse cardiomyocytes were incubated with normal glucose (NG) or high glucose (HG). Male C57BL/6 mice received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Here, we demonstrated that the baseline fluorescence signals of HNO in H9c2 cells were reinforced by both HNO donor Angeli's salt (AS), and the mixture of hydrogen sulfide (H2S) donor sodium hydrogen sulfide (NaHS) and NO donor sodium nitroprusside (SNP), but decreased by HG. Pretreatment with AS significantly reduced HG-induced cell vitality injury, apoptosis, reactive oxygen species (ROS) generation, and hypertrophy in H9c2 cells. This effect was mediated by induction of caveolin-3 (Cav-3)/endothelial nitric oxide (NO) synthase (eNOS) complex. Disruption of Cav-3/eNOS by pharmacological manipulation or small interfering RNA (siRNA) abolished the protective effects of AS in HG-incubated H9c2 cells. In STZ-induced diabetic mice, administration of AS ameliorated the development of diabetic cardiomyopathy, as evidenced by improved cardiac function and reduced cardiac hypertrophy, apoptosis, oxidative stress and myocardial fibrosis without affecting hyperglycemia. This study shed light on how interaction of NO and H2S regulates cardiac pathology and provide new route to treat diabetic cardiomyopathy with HNO. 

Retracted: No

PubPeer comments:
 ![file] ![file] Fig. 7A In fact, Figure 7a is not right. This result is only the background of myocardial tissue, not ROS. After the myocardial tissue is incubated with DHE, ROS is mainly located in the nucleus, rather than the whole cell. The correct picture is shown belowuff1aDOI:10.1371 journal.pone.0048601 ![file] , 
 ![file] , 
 DOI:10.1155 2013 279847 Sivelestat Attenuates Myocardial Reperfusion Injury during Brief Low Flow Postischemic Infusion The **CORRECT FIGURE** is as follows: ![file] ,
TRIP13 Regulates Both the Activation and Inactivation of the Spindle-Assembly Checkpoint
Authors: Hoi Tang Ma
Randy Yat Choi Poon
Journal: Cell Reports (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MAD2; mitosis; mitotic exit; p31(comet); spindle-assembly checkpoint.
Affiliations: Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong., Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong. Electronic address: .

Abstract:  Biochemical studies have indicated that p31(comet) and TRIP13 are critical for inactivating MAD2. To address unequivocally whether p31(comet) and TRIP13 are required for mitotic exit at the cellular level, their genes were ablated either individually or together in human cells. Neither p31(comet) nor TRIP13 were absolutely required for unperturbed mitosis. MAD2 inactivation was only partially impaired in p31(comet)-deficient cells. In contrast, TRIP13-deficient cells contained MAD2 exclusively in the C-MAD2 conformation. Our results indicate that although p31(comet) enhanced TRIP13-mediated MAD2 conversion, it was not absolutely necessary for the process. Paradoxically, TRIP13-deficient cells were unable to activate the spindle-assembly checkpoint, revealing that cells lacking the ability to inactivate MAD2 were incapable in mounting a checkpoint response. These results establish a paradigm of the roles of p31(comet) and TRIP13 in both checkpoint activation and inactivation. 

Retracted: No

PubPeer comments:
 Oncogene published a correction 7 September 2020: https: www.nature.com articles s41388-020-01441-6 According to the authors,  an incorrect image of N-cadherin was included in Figure 5f . This time, Oncogene editors and editorial office had a new opportunity to examine the article, but apparently they did not. Figure 1c: it is very clear that many of the blots presented together in a Western blotting panel do not originate from the same gel experiment. E.g. pFGFR1 and FGFR1 and pERK1 2 and ERK1 2 show very different band shape. Figure 2d: one of the merged images does not correspond to the single staining micrographs. Figure 1e, 3c and 4d: many of the micrographs have been reused across the figures and presented as something else. Figure 1f, 3d and 4e: many of the micrographs have been reused across the figures and presented as something else. ![file] ![file] ![file] ![file] ,
Attenuated strains of Mycobacterium avium subspecies paratuberculosis as vaccine candidates against Johne's disease
Authors: Adel Talaat
Erik W Settles
John A Kink
Journal: Vaccine (2014)
Discipline: IMMUNOLOGY
Keywords: Johne's disease; Live attenuated vaccines; Paratuberculosis.
Affiliations: Pan Genome Systems, Madison, WI 53719, USA; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA., Pan Genome Systems, Madison, WI 53719, USA., Pan Genome Systems, Madison, WI 53719, USA; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. Electronic address: .

Abstract:  Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. Johne's disease has a severe economic impact on the dairy industry in the USA and worldwide. In an effort to combat this disease, we screened several transposon mutants that were attenuated in the murine model of paratuberculosis for the potential use as live attenuated vaccines. Using the murine model, two vaccine candidates (pgs1360, pgs3965 with mutations of fabG2_2 and umaA1, respectively) were at or below the limit of detection for tissue colonization suggesting their low level persistence and hence safety. Prior to challenge, both candidates induced a M. paratuberculosis-specific IFN-γ, an indication of eliciting cell-mediated immunity. Following challenge with a virulent strain of M. paratuberculosis, the two vaccine candidates significantly reduced bacterial colonization in organs with reduced histological scores compared to control animals. In addition, one of the vaccine candidates (pgs3965) also induced IL-17a, a cytokine associated with protective immunity in mycobacterial infection. Our analysis suggested that the pgs3965 vaccine candidate is a potential live-attenuated vaccine that could be tested further in ruminant models of paratuberculosis. The analysis also validated our screening strategy to identify effective vaccine candidates against intracellular pathogens. 

Retracted: No

PubPeer comments:
 Figure 2 has image duplication. Figure 2b and 2c are clearly the same image, yet came from the livers of two different animals which received different vaccine formulations. ,
Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs)
Authors: C J Wu
Z Chen
A Ullrich
M I Greene
D M O&#x27;Rourke
Journal: Oncogene (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: growth factors; cytokines; tyrosine phosphorylation; Signal Regulatory Proteins (SIRPs); EGF
Affiliations: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, PA 19104, USA.

Abstract:  Several growth factors and cytokines, including EGF, are known to induce tyrosine phosphorylation of Signal Regulatory Proteins (SIRPs). Consistent with the idea that increased phosphorylation activates SIRP function, we overexpressed human SIRPalpha1 in U87MG glioblastoma cells in order to examine how SIRPalpha1 modulates EGFR signaling pathways. Endogenous EGFR proteins are overexpressed in U87MG cells and these cells exhibit survival and motility phenotypes that are influenced by EGFR kinase activity. Overexpression of the SIRPalpha1 cDNA diminished EGF-induced phosphoinositide-3-OH kinase (PI3-K) activation in U87MG cells. Reduced EGF-stimulated activation of PI3-K was mediated by interactions between carboxyl terminus of SIRPalpha1 and the Src homology-2 (SH2)-containing phosphotyrosine phosphatase, SHP2. SIRPalpha1 overexpression also reduced the EGF-induced association between SHP2 and the p85 regulatory subunit of PI3-K. Inhibition of transformation and enhanced apoptosis following gamma-irradiation were observed in SIRPalpha1-overexpressing U87MG cells, and enhanced apoptosis was associated with reduced levels of bcl-xL protein. Furthermore, SIRPalpha1-overexpressing U87MG cells displayed reduced cell migration and cell spreading that was mediated by association between SIRPalpha1 and SHP2. However, SIRPalpha1-overexpressing U87MG clonal derivatives exhibited no differences in cell growth or levels of mitogen-activated protein kinase (MAPK) activation. These data reveal a pathway that negatively regulates EGFR-induced PI3-K activation in glioblastoma cells and involves interactions between SHP2 and tyrosine phosphorylated SIRPalpha1. These results also suggest that negative regulation of PI3-K pathway activation by the SIRP family of transmembrane receptors may diminish EGFR-mediated motility and survival phenotypes that contribute to transformation of glioblastoma cells. Oncogene (2000) 19, 3999 - 4010. 

Retracted: No

PubPeer comments:
 Figure 3D. Much more similar than you would expect. https: imgur.com 06IqP7x , 
 Figure 6C. Much more similar than you would expect. https: imgur.com ad2Xmdr , 
 #2 Figure 6C continued. Much more similar than you would expect. https: imgur.com jLXUsmj , 
 #3 Regarding Figure 6C, I agree with the original poster that these smears in 3 lanes appear to be the same. Understanding that the authors may no longer have the original images, could they address how this might affect the conclusions? False color image below. *** ![file] ,