bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1594: Contribution of Stromal Lymphocytes to Lung Cancer Metastasis: Role in Epithelial Mesenchymal Transition
Authors: Salazar Ylia , Huber Magdalena , Schmall Anja , Seeger Werner , Pullamsetti SoniSavai , Savai Rajkumar , Huber Magdalena , Schmall Anja , Seeger Werner , Pullamsetti. SoniSavai 
Published: July 2016

Abstract
The tumor microenvironment and its immune components play a critical role in cancer development, progression, and control. In this study we aim to investigate the role of tumor infiltrating lymphocyte subpopulations in lung cancer progression.
Conditioned media (CM) from co-cultures of human lymphocytes with adenocarcinoma cells (A549) induced the loss of the epithelial markers (E-Cadherin and ZO2 and an increase of mesenchymal markers (vimentin, N-cadherin on mRNA and protein level. In addition, the cells demonstrated a spindled shape-like morphological changes and an increased migratory property. In order to explore the molecular mechanism that led to lymphocyte-induced EMT and migration, we performed a cytokine array from the co-culture CM and found elevated levels of IL-8, IL-16, CCL2 and G-CSF. Furthermore, we observed that lymphocyte-induced EMT was mediated via a TGFβ-independent pathway that involves phosphorylation of ERK1/2.
Notably, this EMT phenotype induction by lymphocytes was independent of the pre-activation of lymphocytes with PMA. Furthermore, in order to identify the specific CD4+ T cell subpopulations (Th0, Th1, Th9 and Th17) responsible for the EMT effect, we generated specific subpopulations from mouse spleen T cells. Interestingly, we observed that Th9 and Th17 subpopulation CM led to EMT and increased migratory phenotype in mouse lung cancer cell lines. Additionally, we identified the T lymphocyte secretory cytokine, IL9, as responsible for the Th9 induced EMT and migratory phenotype of lung cancer cells.
This study reveals that specific T lymphocyte subpopulations, i.e. Th9 and Th17 induce EMT in lung cancer cells, suggesting T cell regulated mechanisms of metastasis.
Citation Format: Ylia Salazar, Magdalena Huber, Anja Schmall, Werner Seeger, SoniSavai Pullamsetti, Rajkumar Savai, Magdalena Huber, Anja Schmall, Werner Seeger, SoniSavai Pullamsetti. Contribution of Stromal Lymphocytes to Lung Cancer Metastasis: Role in Epithelial Mesenchymal Transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1594.
Abstract 1597: Claudin-1 expression promote TNF-a-induced epithelial-mesenchymal transition and growth in colorectal adenocarcinoma cells
Authors: Bhat Ajaz Ahmad , Ahmad Rizwan , Singh Amar B. , Dhawan Punita 
Published: July 2016

Abstract
Epithelial-mesenchymal transition (EMT) is an important mechanism in colorectal cancer progression and malignancy. Importantly, inflammatory mediators are critical constituents of the local tumor environment and an intimate link between colon cancer progression and inflammation in now validated. Notably, we and others have previously reported key role of the deregulated claudin-1, a tight junction protein, in colon carcinogenesis including colitis-associated colon cancer (CAC). Of interest, the increase in claudin-1 expression in CAC was found to be associated with the inflammatory epithelium. We have further demonstrated that inflammation induced by DSS (Dextran Sodium Sulfate) administration promotes colon cancer in APCmin/Claudin-1 transgenic mice. However, what role claudin-1 plays in inflammation-induced colon cancer remains unclear. In current study, we tested the causal significance of claudin-1 expression in inflammation-associated colon cancer using colon cancer cells subjected to TNF-αα, a pro-inflammatory cytokine, treatment. HT29 colon adenocarcinoma cells cultured in the presence of TNF-α (10ng/ml), demonstrated a sharp decrease in E-cadherin expression and an increase in Vimentin expression versus control cells suggesting TNF-αα treatment induced EMT. Also, significant increase in cell proliferation and wound healing was observed in TNF-α treated cells at 24 and 48 hours of TNF-αα treatment (versus control cells). Interestingly, TNF-αα treatment also upregulated (and delocalized) claudin-1 expression in a time-dependent manner. An increase in the phosphorylation of Erk1/2 and Src, signaling associated with colon cancer survival and transformation, in TNF-αα treated cells further correlated with our published observations that claudin-1 expression promotes these signaling pathways in colon cancer cells. In support, shRNA-mediated inhibition of claudin-1 expression in HT-29 cells largely abrogated the effects of TNF-αα treatment including proliferation, p-erk and p-Src expression. Also, TNF-αα induced EMT was largely suppressed in the absence of claudin-1 expression. Taken together, our data confirm the previously described key role of claudin-1 in regulating tumorigenic abilities of colon cancer cells and further highlights a key role of claudin-1 in inflammation-induced colorectal cancer growth and progression. We predict claudin-1 expression can serve as a biomarker to predict CAC progression and malignancy.
Citation Format: Ajaz Ahmad Bhat, Rizwan Ahmad, Amar B. Singh, Punita Dhawan. Claudin-1 expression promote TNF-a-induced epithelial-mesenchymal transition and growth in colorectal adenocarcinoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1597.
Abstract 1608: Resistin promotes cancer progression through induction of mesenchymal phenotypes and stem cell-like properties in breast cancer
Authors: Yuan Shyng-Shiou F. , Wang Chie-Hong 
Published: July 2016

Abstract
Growing evidence indicates that resistin plays a role in insulin resistance, obesity, inflammation, coronary artery disease, atherosclerosis and malignancies. In this study, we have explored the effects and mechanisms of resistin in promoting breast cancer progression. High serum resistin levels were positively correlated with tumor stage, tumor size and lymph node metastasis in breast cancer patients. Resistin treatment modulated the expression of epithelial-mesenchymal transition (EMT) regulators and enhanced the migratory, invasive and anti-anoikis activities in breast cancer cells. Additionally, resistin treatment promoted the formation of mammospheres and the expression of pluripotency factors (sox2, nanog and oct4). STAT3 specific inhibitor, stattic, was able to abolish the resistin mediated enhancements of cell motilities and stem cell-like properties. Using in vivo model, we found that resistin markedly enhance metastasis and tumor growth. Taken together, our data clearly demonstrated that resistin promotes cancer progression through induction of EMT and stemness by activating TLR4/STAT3 signaling in breast cancer.
Citation Format: Shyng-Shiou F. Yuan, Chie-Hong Wang. Resistin promotes cancer progression through induction of mesenchymal phenotypes and stem cell-like properties in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1608.
Abstract 1614: Identification of FBXL4 as a bone metastasis-associated gene in prostate cancer
Authors: Stankiewicz Elzbieta , Mao Xueying , Mangham D Chas , Xu Lei , Fisher Gabrielle , North Bernard , Moller Henrik , Scardino Peter , Cuzick Jack , Berney Dan , Lu Yong-Jie 
Published: July 2016

Abstract
Prostate cancer (PCa) is the most common cancer among men in Western developed countries. While the majority of PCa diagnosed by PSA screening are indolent, advanced and metastatic disease has a significant mortality and morbidity. Bone metastases are extremely common in PCa and identification of bone metastasis associated genes may provide insights into PCa progression and assist in finding new drug targets. However, the genetic study of bone metastases is very limited due to the difficulty of sampling. By analyzing PCa bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1-16.2, containing the FBXL4 gene, which was confirmed in a separate and larger series of bone metastatic samples by fluorescence in situ hybridization (FISH). Loss of FBXL4 was also detected in primary PCa, although at a significantly lower frequency than in bone metastases, and it was highly associated with prognostic factors including high Gleason score, clinical stage, PSA and extent of disease, as well as poor patient survival in conservatively-managed localized PCa, suggesting that loss of FBXL4 contributes to PCa progression. We also demonstrated that FBXL4 deletion is detectable in circulating tumor cells, making it a potential disease prognostic or progression monitoring biomarker by ‘liquid biopsy’. Consistent with loss of FBXL4 being associated with aggressive tumors, we demonstrated in vitro that FBXL4 plays a role in regulating the migration and invasion of PCa cells. Therefore, FBXL4 is a potential novel PCa suppressor gene, which may prevent cancer progression and bone metastasis through controlling cell invasion.
Citation Format: Elzbieta Stankiewicz, Xueying Mao, D Chas Mangham, Lei Xu, Gabrielle Fisher, Bernard North, Henrik Moller, Peter Scardino, Jack Cuzick, Dan Berney, Yong-Jie Lu. Identification of FBXL4 as a bone metastasis-associated gene in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1614.
Abstract 1615: Metastasis suppression by KP54 and non-KP54 kisspeptins
Authors: Hampton Kelsey R. , Pounds Keke M. , Trembath Andrew P. , Welch Danny R. 
Published: July 2016

Abstract
The KISS1 metastasis suppressor blocks metastasis by inhibiting colonization at secondary sites. In order to suppress metastasis, KISS1 must be secreted and cleaved by furin into kisspeptins. Kisspeptin-54 (KP54, K67 to F121) binds a G-protein coupled receptor, KISS1R, and the mechanism of metastasis suppression has been assumed to be through KP54 binding with KISS1R. However, since KISS1 is cleaved extracellularly, and since none of the cells tested express KISS1R, an alternate hypothesis is required - another kisspeptin is responsible for suppressing metastasis. To test this hypothesis, we engineered all ten of the possible kisspeptins based upon predicted dibasic cleavage sites (M1-Q145; M1-R56; M1-R67; M1-R124; R56-R66; R67-F121; R56-F121; R56-Q145; R67-Q145; R124-Q145). The (KISS1 Manufactured Peptides, or KMP) each contained the same secretion signal as nascent KISS1 and were designated KMP1 to KMP10 respectively. Each KMP was expressed individually in B16-F10 melanoma cells. Following intravenous injection, experimental lung metastases were quantified. While KP54 expression suppressed metastasis, other KMP lacking the KISS1R binding motif also suppressed metastasis as or more effectively (p&lt;0.05). In vitro, cell lines expressing suppressor KMP inhibited motility, increased mitochondrial biomass, and elevated levels of oxidative phosphorylation (phenotypes previously correlated with KISS1 function). In particular, KMP2 (M1 - R56) completely suppressed metastasis. Collectively, these data demonstrate that the mechanism of action for metastasis suppression by KISS1 does not necessarily require activation of KISS1R, and also suggests the existence of additional receptors.
Support: CA134981, Natl Fndn Cancer Res, Komen SAC11037, KS Bioscience Auth, P30-CA168524, Steiner Family Fund for Metastasis Research.
Citation Format: Kelsey R. Hampton, Keke M. Pounds, Andrew P. Trembath, Danny R. Welch. Metastasis suppression by KP54 and non-KP54 kisspeptins. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1615.
Abstract 1625: CUB domain-containing protein 1 (CDCP1) promotes metastatic phenotype in pancreatic ductal adenocarcinoma
Authors: Kim Sunnie , Emerling Brooke , Hopkins Benjamin , Loughran Ryan , Naranjos Salva , Cantley Lewis 
Published: July 2016

Abstract
CUB domain-containing protein 1 (CDCP1) is a transmembrane glycoprotein that is overexpressed and highly tyrosine phosphorylated in multiple cancer types including pancreatic ductal adenocarcinoma (PDAC), a highly lethal disease. CDCP1 has been implicated in the promotion of metastases, namely cancer cell migration, invasion, and resistance to anoikis. In addition, prior studies in other cancer cell lines have shown that hypoxia inducible factors (HIF-1α and HIF-2α), which are key regulators of metastasis, induce both expression of CDCP1 and phosphorylation at tyrosine 734. The role of CDCP1 and the mechanisms that regulate CDCP1 still need further elucidation in PDAC.
In this study, we demonstrated that CDCP1 is highly expressed and tyrosine phosphorylated in PDAC cell lines MiaPaCa2, PaTu89902, and Panc-1 cell lines compared to the non-tumorigenic pancreatic ductal cell line HPNE. shRNA knockdown of CDCP1 showed a reduction in the phosphorylation of Src and PKC-delta. To determine whether HIF regulates CDCP1 in PDAC, we used PDAC cell lines that stably express shRNAs targeting HIF-1α and HIF-2α. Hypoxia induced an increase in CDCP1 expression in a HIF-1α-dependent fashion. Additionally, CDCP1 knockdown in PaTu8902, a highly metastatic PDAC line, impaired cancer cell invasion by transwell invasion assay but did not show resistance to anoikis by soft agar assay. To validate our data in vivo, we performed intra-pancreatic injection of shCDCP1 PaTu8902 cells and scramble control transfected with GFP/luciferase into nude mice. Live imaging demonstrated that 2 weeks after initial injection resulted in decreased tumor establishment in mice injected with the shCDCP1 cell line compared to control. We propose that CDCP1 expression and tyrosine phosphorylation in PDAC is mediated by hypoxia inducible factors and that CDCP1 confers invasive properties in vitro and may play a role in initial tumor establishment in vivo. Based on these results, CDCP1 is a promising novel target for PDAC.
Citation Format: Sunnie Kim, Brooke Emerling, Benjamin Hopkins, Ryan Loughran, Salva Naranjos, Lewis Cantley. CUB domain-containing protein 1 (CDCP1) promotes metastatic phenotype in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1625.
Abstract 1639: CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer
Authors: Wright Heather , Arulmoli Janahan , Motazedi Maryam , Nelson Luke , Razorenova Olga 
Published: July 2016

Abstract
Triple negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks the estrogen, progesterone, and HER2 receptors and is resistant to targeted and hormone therapies. TNBCs express high levels of the transmembrane glycoprotein, CUB-domain containing protein 1 (CDCP1), which has been correlated with the aggressiveness and poor prognosis of multiple carcinomas. Full-length CDCP1 (flCDCP1) can be proteolytically cleaved, resulting in a cleaved membrane-bound isoform (cCDCP1). CDCP1 is phosphorylated by Src family kinases in its full-length and cleaved states, which is important for its pro-metastatic signaling. We observed that cCDCP1, compared to flCDCP1, induced a dramatic increase in phosphorylation of the migration-associated proteins: PKCδ, ERK1/2, and p38 MAPK in HEK 293T. In addition, only cCDCP1 induced migration of HEK 293T cells and rescued migration of the TNBC cell line, MDA-MB-231, expressing shRNA against CDCP1. Importantly, we found that only cCDCP1 is capable of dimerization, which can be blocked by expression of the extracellular portion of cCDCP1 (ECC), indicating that dimerization occurs through CDCP1's ectodomain. We found that ECC inhibited phosphorylation of PKCδ and migration of TNBC cells in 2D culture. Furthermore, ECC induced morphological changes, inhibited proliferation, and stimulated apoptosis of TNBC cells in 3D culture, indicating that the cCDCP1 dimer is an important contributor to TNBC aggressiveness. These studies have important implications for development of a therapeutic to block CDCP1 activity and TNBC metastasis.
Citation Format: Heather Wright, Janahan Arulmoli, Maryam Motazedi, Luke Nelson, Olga Razorenova. CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1639.
Abstract 1640: SORBS1-related multiprotein complex regulates metastasis of cancer
Authors: Cho Woo-Cheol , Ku Ja-Lok 
Published: July 2016

Abstract
Purpose: CAP (Cbl-associated protein), also known as Sorbin and SH3 domain-containing protein 1 is encoded by the SORBS1 gene. These proteins contain a conserved sorbin homology (SOHO) domain and three SH3 domains. CAP is an adaptor protein that has been associated with the actin cytoskeleton, signaling through receptor tyrosine kinases and cell adhesion. Although, CAP is proven to have many known functions, this protein is only reported in specific field of signaling pathway. Cell adhesion and actin dynamics which have been supposed to participate in CAP are crucial factors of cancer metastasis. The role of CAP has been described in the literature, although their specific roles remain to be clarified in cancer.
Methods and materials: Colorectal cancer cell lines were transduced by lentivirus containing shRNA plasmid (shSORBS1 plasmid). To elucidate function of SORBS1 as regulator of cancer metastasis, western blotting, cell migration assay and immunoprecipitation assays were performed.
Conclusion: According to the several reports of SORBS1 function, phosphorylation of ERK and mTOR was identified. Although ERK phosphorylation were not changed in normal condition, there were different aspects between control group and SORBS1 knockdown group with insulin treatment. Moreover, mTOR phosphorylation of SORBS1 knockdown group was less in the control group than in the normal condition.
Immunoprecipitation of SORBS1 was performed to search for the binding compounds. We chose the AHNAK protein as the convincing candidate protein related with SORBS1. Several studies reported that AHNAK protein is related to proliferation and EMT by binding of specific signaling molecules. Indeed, there were remarkable differences of invasiveness ability between control group and knockdown group.
Citation Format: Woo-Cheol Cho, Ja-Lok Ku. SORBS1-related multiprotein complex regulates metastasis of cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1640.
Abstract 1643: p53 family and oncogenic signaling in cancer metastasis
Authors: Xiao Zhi-Xiong , Lv Tao , Wan Yang , Bergholz Johann , Zhang Yujun 
Published: July 2016

Abstract
The tumor suppressor protein p53 is mutated in over 50% of human cancers. Multiple lines of evidence have shown that mutant p53 not only loses its ability to inhibit tumorigenesis, but also gains pro-metastatic functions. However, the molecular mechanisms underlying these effects are still not totally understood. In this study, we demonstrate that the p53 hotspot point mutant, p53(R273H), potently induces cell spreading, migration, and invasion. At the molecular level, p53(R273H) regulates the DLX2-NRP2 pathway in promoting cancer cell migration in vitro and metastasis in vivo. Interestingly, p53(R273H) strongly inhibits tumor cell growth in vitro and in xenograft nude mice model. In addition, we show that p53-related p63 inhibits Erk2 signaling in regulating cell migration/invasion.
Citation Format: Zhi-Xiong Xiao, Tao Lv, Yang Wan, Johann Bergholz, Yujun Zhang. p53 family and oncogenic signaling in cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1643.
Abstract 1668: Bouvardinis a radiation modulator with a novel mechanism of action
Authors: SU. Tin tin 
Published: July 2016

Abstract
Protein synthesis is essential for growth, proliferation and survival of cells. Translation factors are overexpressed in many cancers and their experimental inhibition curbs cancer growth in preclinical models. Differential regulation of translation also occurs upon exposure to cancer-relevant stresses such as hypoxia and ionizing radiation (IR). The failure to regulate translation has been shown to interfere with recovery after genotoxic stress. These findings suggest that modulation of translation, alone or in conjunction with genotoxins, may be therapeutic in oncology. Yet, only two drugs that directly inhibit translation are FDA-approved for oncology use today. We described before the identification of protein synthesis inhibitor bouvardin in a screen for small molecule enhancers of IR in Drosophila melanogaster. Bouvardin was independently identified in a screen for selective inhibitors of engineered human breast cancer stem cells. Here we report the effect of bouvardin in preclinical models of head and neck cancer (HNC) and glioma, two cancer types for which IR is a key therapy choice. Our data show for the first time that bouvardin blocked translation elongation on human ribosomes and suggest that it did so by blocking the dissociation of elongation factor 2 from the ribosome. Bouvardin enhanced the induction of clonogenic death by IR in HNC and glioma cells, although by different mechanisms. Bouvardin enhanced the anti-tumor effect of IR in HNC tumor xenografts in mice. These data suggest that inhibition of translation elongation, particularly in combination with IR, may be a promising treatment option for cancer.
Citation Format: Tin tin SU. Bouvardinis a radiation modulator with a novel mechanism of action. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1668.