bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1118: Stress-induced differential Survivin release in prostate cancer health disparities
Authors: Khan Salma , Turay David , Jutzy Jessica Ms , Aspe Jonathan R. , Sanchez Tino W. , Mirshahidi Saeid , Casiano Carlos A. , Wall Nathan R. 
Published: May 2015

Abstract
African-American men have the highest rate of prostate cancer (PCa) incidence in the U.S. In addition, their prostate cancer mortality rate is more than twice as high as the rate for white Americans. The causes of higher rates of prostate cancer among African-American males are largely unknown. Many studies are underway to unravel the impact of a wide variety of potential risk factors, including dietary and other lifestyle differences, occupational exposures, hormonal and genetic differences. Several lines of evidence suggest that one of the main events associated with the conversion to an aggressive phenotype is increased resistance to apoptosis (3) mainly due to upregulation of antiapoptotic genes, including Bcl-2, Bcl-XL, Mcl-1, and Survivin. Recently, we reported that Survivin is released in PCa sera and found to be in the exosomes. Therefore, we speculate that Survivin could be a potential target protein released differentially in prostate cancers in African American (AA) and Caucasian (CC) populations in response to stress. In this study, we have collected serum samples from prostate cancer patients of AA and CC, measured Survivin levels by ELISA. Exosome islation was perfomed by Exoquick approach and quantified by acetylcholinesterase activity assays. We have applied an in-vitro approach to compare the differences between cancer cell lines derived from AA (MDA-MB-PCa) and CC (PC3) patients in terms of stress and stress activated Survivin release by exosomes. Under oxidative stress and drug treatments, we have identified Survivin highly expressed in exosome derived from MDA-MB-PCa compared to PC3 cell lines. In addition, we found a relative overexpression of Survivin protein in AA-PCa compared to CC-PCa both in sera and exosomes. Based on our data, Survivin may be a key stress-induced protein in AA-PCa patients. It is possible that attempts to block Survivin release will not only interrupt the cancer proliferation and interfere with anti-apoptotic pathways, thus preventing cancer progression.
Citation Format: Salma Khan, David Turay, Jessica Ms Jutzy, Jonathan R. Aspe, Tino W. Sanchez, Saeid Mirshahidi, Carlos A. Casiano, Nathan R. Wall. Stress-induced differential Survivin release in prostate cancer health disparities. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1118. doi:10.1158/1538-7445.AM2014-1118
Abstract 1121: Extracellular matrix-integrin B1 signaling is a major mediator of epithelial-to-mesenchymal transition and contributes to prostate cancer invasion and metastasis
Authors: Bugiel Steven R. , McKittrick Elisabeth , Zhao Huijun , Howe Grant A. , Addison Christina L. 
Published: May 2015

Abstract
Within North America, prostate cancer is the most commonly diagnosed cancer in men with devastating implications deriving from metastasis, particularly those established in the bone. We have elucidated mechanisms by which prostate cancer undergoes metastasis with particular focus on the relationship between extracellular-matrix binding proteins, Integrin B1 (ITGB1) and epithelial-to-mesenchymal transition (EMT). Previous results in the laboratory suggested that prostate tumor cells depleted of ITGB1 were unable to form colonies in soft agarose and were impaired in their invasive abilities in vitro. In order to determine the possible mechanisms by which ITGB1 controlled these phenotypes, we performed numerous genetic techniques including siRNA targeted depletion of ITGB1 and subsequent profiling of pathway specific message RNA by RTqPCR to monitor the effects ITGB1 depletion on factors known to control EMT which is also associated with cell invasion. We found that prostate tumor cells depleted of ITGB1 had altered expression of numerous genes associated with EMT or cell invasion, many of which have been validated by RT-qPCR and western blot. In particular, a protease inhibitor SERPINE1 also known as Plasminogen Activator Inhibitor 1 (PAI-1) which is associated with EMT has been established as a target of ITGB1 regulation, in part via the ability of ITGB1 to regulate upstream factors associated with SERPINE1 expression such as TGFB2. Of particular interest to prostate cancer bone metastasis, we further found that collagen I interacting with ITGB1 significantly upregulated this pathway, and given the known role of EMT in mediating resistance to anti-cancer agents, this finding could help elucidate novel targets for the development of new drugs to treat prostate cancer bone metastasis.
Citation Format: Steven R. Bugiel, Elisabeth McKittrick, Huijun Zhao, Grant A. Howe, Christina L. Addison. Extracellular matrix-integrin B1 signaling is a major mediator of epithelial-to-mesenchymal transition and contributes to prostate cancer invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1121. doi:10.1158/1538-7445.AM2014-1121
Abstract 1122: Tetrandrine induces expression of growth/differentiation factor-15 and promoted terminal differentiation of PCa cells
Authors: Koul Sweaty , Koul Hari K. 
Published: May 2015

Abstract
Tetrandrine (Tet) is a naturally derived bis-benzylisoquinoline alkaloid, from S tenrandra, a herb that has been used in Chinese medicine for its anti-inflammatory, immunologic and antiallergenic effects. Results from our laboratory show that Tetrandarine blocks prostate cancer growth, promotes cell cycle arrest and induces apoptosis in a time and concentration dependent manner. In the present study we performed un-biased gene expression analysis of LNCaP cells following treatment with Tet. Analysis of gene expression revealed that GDF-15 was one of the most highly expressed cytokines following treatment of LNCaP cells with Tet. The gene expression results were further confirmed in relative quantitative PCR and Real time PCR assays, as was protein expression of GDF-15 confirmed by Western blot analysis. Our results, in light of the role of GDF-15 as a macrophage inhibitory factor as well as prostate epithelial differentiating factor, suggest that Tet may serve as a useful agent to promote prostate epithelial differentiation and inhibit tumor macrophage infiltration. Additional studies revealed that Treatment of PCa cells with Tet inhibited cell migration and invasion and suppressed EMT. Taken together we conclude that Tet by regulating GDF-15 expression may serve as an inhibitor of Prostate cancer cell progression and metastasis.
(Financial Support: Supported in part by NIH/NCI R01CA161880 (PI:H.Koul); VA Merit Award 01BX001258 (PI:H.Koul); Carroll W. Feist endowed Cahir and LSUHSC Chair Commitment Funds)
Citation Format: Sweaty Koul, Hari K. Koul. Tetrandrine induces expression of growth/differentiation factor-15 and promoted terminal differentiation of PCa cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2014-1122
Abstract 1123: Fucosylated TGF-ß receptors transduce a signal for epithelial-mesenchymal transition in colorectal cancer cells
Authors: Takimoto Rishu , Hirakawa Masahiro , Tamura Fumito , Yoshida Makoto , Ono Michihiro , Sato Yasushi , Osuga Takahiro , Kato Junji 
Published: May 2015

Abstract
Background: Transforming growth factor-ß (TGF-ß) is a major inducer of epithelial-mesenchymal transition (EMT) in different cell types. TGF-ß-mediated EMT is thought to contribute to tumor cell spread and metastasis. Sialyl Lewis antigens synthesized by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilized as tumor markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-ß is unclear.
Methods: CRC cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion, and migration assays. The expression and phosphorylation status of TGF-ß downstream molecules were analyzed by western blot. Fucosylation of TGF-ß receptor was examined by lectin blot analysis.
Results: Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TGF-ß receptor and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT.
Citation Format: Rishu Takimoto, Masahiro Hirakawa, Fumito Tamura, Makoto Yoshida, Michihiro Ono, Yasushi Sato, Takahiro Osuga, Junji Kato. Fucosylated TGF-ß receptors transduce a signal for epithelial-mesenchymal transition in colorectal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1123. doi:10.1158/1538-7445.AM2014-1123
Abstract 1126: Tristetraprolin inhibits Twist1-induced cancer cell migration
Authors: Cho Wha J. , Yoon Nal A. , Vo Mai-Tram , Min Young Joo , Park Jeong Woo 
Published: May 2015

Abstract
Epithelial-Mesenchymal Transition (EMT) enhances tumor cell migration. However, detail mechanisms for the regulation of EMT are not well known. Tristetraprolin (TTP) is an AU-rich element (ARE) binding protein that can promote the decay of the transcripts. This study demonstrates that TTP plays a critical role in EMT process. Overexpression of TTP in ovarian cancer cells decreased the expression of mesenchymal markers (N-cadherin and Vimentin), increased the expression of epithelial marker (E-cadherin), and inhibited cell migration and invasion activities. On the contrary, inhibition of TTP by siRNA decreased the expression of E-cadherin, increased the expression of N-cadherin and Vimentin, and promoted cell migration and invasion. The cDNA microarray analysis revealed that Twist1 was significantly down-regulated in TTP-overexpressed cells. Twist1 mRNA contains ARE within its 3′-UTR and TTP enhances the decay of Twist1 mRNA through binding to its 3′-UTR. In addition, TTP directly bound to the ARE of Twist1 mRNA by EMSA assay. Ectopic expression of Twist1 gene without 3′UTR blocked the inhibitory of TTP on the EMT. We also observed enhanced levels of Twist1 and reduced TTP levels in human ovarian adenocarcinoma. Collectively, our data indicate that TTP conducts anti-metastatic activity by down-regulating Twist1, presenting a novel mechanism of TTP-mediated regulation of tumor metastasis.
Citation Format: Wha Ja Cho, Nal Ae Yoon, Mai-Tram Vo, Young Joo Min, Jeong Woo Park. Tristetraprolin inhibits Twist1-induced cancer cell migration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1126. doi:10.1158/1538-7445.AM2014-1126
Abstract 1127: Snail inhibits lung colonization and metastasis in luminal type A breast cancer cells
Authors: Lin Shih-Pei , Hung Shih-Chieh 
Published: May 2015

Abstract
Breast cancer is the most common malignant disease in Western women. In these patients, it is not the primary tumor, but its metastases at distant sites that are the main cause of death. Breast cancer include five biologically distinct subgroups including Luminal A (ER+ ck8h/ck18h), Luminal B (ER+ ck8l/ck18l), Basal (ER- ck5+/ck17+) and ERBB2+ (ER- ERBB2+ GFRBP7+) and normal breast-like types. The time to distant metastasis and overall survive rate were distinct among these subgroups. Luminal type has the best prognosis, while basal type or ERBB2+ has the worst prognosis. What mechanism involves in this difference remains to be elucidated. In the current study, we demonstrated (1) Luminal type A tumor such as MCF7 when overexpressed with active mutant form of Snail gene increased in the expression of markers for epithelial mesenchymal transition such as Vimentin, N-cadherin and Fibronectin but decreased in the expression of E-cadherin compared to cells overexpressed with control vectors of wild type Snail gene. Moreover, these cells increased in the capacity of migration and invasion. (2) While, MCF7 overexpressed with active mutant form of Snail decreased in the ability to survive and form sphere in serum-free medium, the in vitro colonization, and were unable to metastasize to lung.Therefore, the elucidation of the differences in molecules or signaling pathways involve in controlling migration, invasion and distant metastasis may have a therapeutically beneficial effect on breast cancer treatment.
Citation Format: Shih-Pei Lin, Shih-Chieh Hung. Snail inhibits lung colonization and metastasis in luminal type A breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1127. doi:10.1158/1538-7445.AM2014-1127
Abstract 1133: Partial EMT, hybrid epithelial-mesenchymal phenotype and epithelial plasticity: role of (miR-200/ZEB) loop
Authors: Jolly Mohit Kumar , Lu Mingyang , Levine Herbert , Onuchic Jose N. , Ben-Jacob Eshel 
Published: May 2015

Abstract
Epithelial to Mesenchymal Transition (EMT) and Mesenchymal to Epithelial Transition (MET) are critical for embryonic development and tissue repair. Aberrantly regulated transitions are also implicated in cancer metastasis. The core regulatory genetic network for these transitions appears to allow for the existence of a hybrid epithelial/mesenchymal phenotype (E/M). Such hybrid cells are seen during wound healing and branching morphogenesis, and have mixed epithelial and mesenchymal characteristics, which enable them to migrate collectively. The core regulatory network for the cell fate determination between these three phenotypes is composed of two highly interconnected mutual-inhibition feedback circuits - miR-34/SNAIL and miR-200/ZEB. Here we applied a novel theoretical framework to model the microRNA-based regulation to study this core regulatory unit. More specifically, we looked into the functions of the two loops in isolation, and subsequently of the combined unit when the two loops are integrated into the full regulatory circuit. We found that miR-200/ZEB forms a tristable circuit that acts as a ternary decision making switch, driven by miR-34/SNAIL that is a monostable loop which acts as noise-buffering integrator of internal and external signals that induce or inhibit EMT/MET. Our results are corroborated by recent experiments indicating the (miR-200/ZEB) to be the commitment point and decision making loop (eg. Cells don't revert to epithelial phenotype on removal of EMT-inducing signal, if ZEB expression has been turned on.) .We associate the three stable states of the miR-200/ZEB circuit to different phenotypes - (1,0) - (high miR-200)/(low ZEB) - epithelial, (0,1) - (low miR-200)/(high ZEB) - mesenchymal, and (1/2,1/2) - (medium miR-200)/(medium ZEB) - hybrid. Thus, we propose that the hybrid epithelial - mesenchymal phenotype has concurrent expression of both miR-200 and ZEB. Our hypothesis is consistent with recent experimental studies (e.g. ZEB expression measurements in collectively migrating cells), and also explains the lack of hybrid phenotype observed during MET in colonization and induced pluripotent stem cells (iPSCs). We also present testable predictions of dynamic gene expression during complete and partial transitions (EMT/MET).
Citation Format: Mohit Kumar Jolly, Mingyang Lu, Herbert Levine, Jose N. Onuchic, Eshel Ben-Jacob. Partial EMT, hybrid epithelial-mesenchymal phenotype and epithelial plasticity: role of (miR-200/ZEB) loop. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1133. doi:10.1158/1538-7445.AM2014-1133
Abstract 1137: Bub1 is a key regulator of TGF-β signaling
Authors: Nyati Shyam , Schinske-Sebolt Katrina , Pitchiaya Sethuramasundaram , Chekhovskiy Katerina , Chator Areeb , Chaudhry Nauman , Dosch Joseph , Dort Marcian E. Van , Varambally Sooryanarayana , Kumar-Sinha Chandan , Nyati Mukesh K. , Ray Dipankar , Walter Nils G. , Yu Hongtao , Ross Brian D. , Rehemtulla Alnawaz 
Published: May 2015

Abstract
The transforming growth factor-beta (TGF-β) family of cytokines regulates many processes such as immune suppression, angiogenesis, wound healing and epithelial to mesenchymal transition (EMT. Early in tumorigenesis, when epithelial cells retain exquisite growth sensitivity to this ligand, TGF-β signaling elicits a tumor suppressing activity. However, transformed cells become refractory to TGF-β-mediated growth inhibition and acquire a phenotype wherein the intracellular signaling circuitry of the cells is altered, leading to tumorigenic and metastatic effects in response to TGF-β exposure. Although TGF-β activating pathways have been studied, the molecular participants are poorly defined. Here we identify budding uninhibited by benzimidazoles-1 (Bub1) as an integral component of canonical and non-canonical TGF-β signaling pathways, where Bub1 is required for TGFBRI-TGFBRII complex formation and activation. Bub1-depleted cells exhibited reductions in TGF-β dependent Smad2/3 phosphorylation, recruitment of Smad2/3 to the TGFBRI-II complex, PI3K/Akt and p38MAPK activation, Smad binding element driven promoter activity (SBE4-Luc), and invasion and migration. Furthermore, a targeted small molecule inhibitor of Bub1 kinase activity (2OH-BNPP1), as well as an inactive kinase mutant of Bub1, abrogated ligand mediated TGF-β signaling and phenotypic response. These studies demonstrate a role for the Bub1 kinase in mediating TGF-β dependent signaling beyond its established function in cell-cycle regulation and chromosome cohesion and uncover the underlying basis for the pleiotropic cellular response commonly observed upon activation of the pathway.
Citation Format: Shyam Nyati, Katrina Schinske-Sebolt, Sethuramasundaram Pitchiaya, Katerina Chekhovskiy, Areeb Chator, Nauman Chaudhry, Joseph Dosch, Marcian E. Van Dort, Varambally, Kumar-Sinha, Nyati, Ray, Walter, Sooryanarayana Varambally, Chandan Kumar-Sinha, Mukesh K. Nyati, Dipankar Ray, Nils G. Walter, Hongtao Yu, Brian D. Ross, Alnawaz Rehemtulla. Bub1 is a key regulator of TGF-β signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1137. doi:10.1158/1538-7445.AM2014-1137
Abstract 1145: Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor progression via Twist1 upregulation
Authors: Zhao Dekuang , Besser Alexandra H. , Zhou Wen , Wander Seth A. , Sun Jun , Durante Michael , Hong Feng , Wang Bin , Ince Tan , Briegel Karoline , Slingerland Joyce M. 
Published: May 2015

Abstract
p27 is a cell cycle regulator that acts largely to restrain normal cell growth. It is rarely mutated or deleted in human cancers, but is often degraded or mislocalized to the cytoplasm in aggressive tumors. Phosphorylation at T157 or T198 by different PI3K effector kinases leads to p27 cytoplasmic accumulation and enhanced cell motility and invasion in part via effects on the actin cytoskeleton, which are independent of its cell cycle role. However, the functional contributions of C-terminally phosphorylated, cytoplasmic p27 to cancer progression remain poorly understood. Targeted inhibition of PI3K/mTOR impaired tumor cell motility and metastasis via modulation of p27 in a bone metastatic model (Wander, S. et al. BCRT 2013). We observed that p27 knockdown in highly metastatic cancer lines with high levels of cytoplasmic p27pT157pT198 reverted EMT and impaired tumor cell invasion in vitro and metastasis in vivo. This led us to investigate whether PI3K-activated, phosphorylated p27 may function as a novel EMT regulator. A cell cycle defective (CK-) and double phosphomimetic p27 mutant (T157D/T198D or DD) was introduced into immortal human mammary epithelial cells with low PI3K activity. This revealed a novel, oncogenic function of p27 in regulating tumor progression, in that p27CK-DD induced epithelial-mesenchymal transition (EMT) and soft agar colony formation. p27CK-DD also increased motility, invasion and formation of metastasis in bladder and breast cancer models. A RT-PCR screen for potential p27-induced EMT mediators revealed a 20-fold increase in expression of the Twist1 transcription factor in p27CK-DD-transduced cells. Knockdown of Twist reversed the p27CK-DD-mediated increase in EMT marker expression. p27 knockdown rapidly attenuated Twist1-promoter activity and reduced Twist1 mRNA levels and also increased E-cadherin expression in metastatic cells, suggesting that Twist1 may play a critical role in p27CK-DD-induced EMT. These data extend our understanding of p27 function in human cancer and suggest that PI3K deregulated p27 may promote EMT and tumor metastasis through transcriptional activation of TWIST1.
Citation Format: Dekuang Zhao, Alexandra H. Besser, Wen Zhou, Seth A. Wander, Jun Sun, Michael Durante, Feng Hong, Bin Wang, Tan Ince, Karoline Briegel, Joyce M. Slingerland. Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor progression via Twist1 upregulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1145. doi:10.1158/1538-7445.AM2014-1145