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pancreatic cancer EMT

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https://www.readbyqxmd.com/read/29340057/aberrant-expression-of-styk1-and-e-cadherin-confer-a-poor-prognosis-for-pancreatic-cancer-patients
#1
Luguang Chen, Chao Ma, Yun Bian, Chengwei Shao, Tiegong Wang, Jing Li, Xiaodan Chong, Li Su, Jianping Lu
Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29331423/thymidylate-synthase-prompts-metastatic-progression-through-the-dtmp-associated-emt-process-in-pancreatic-ductal-adenocarcinoma
#2
Muxing Kang, Wen Zheng, Qing Chen, Wenjie Qin, Pengping Li, Shifei Huang, Yizhao Zhou, Lantian Wang, Haolei Cai, Wenjie Lu, Biao Jiang, Qingqu Guo, Jian Chen, Dylan Wan, Jianyu Rao, Yulian Wu
As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has been shown to be an effective therapy for human cancers. However, the genuine effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We systemically assessed the prognostic value and whether TS associated with malignant progression in PDA. Protein and mRNA expression level of TS were evaluated in en bloc PDA samples, the prognostic effect of TS expressed in cytoplasm or cytonuclear was determined separately in the first time...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29329547/microfluidic-co-culture-of-pancreatic-tumor-spheroids-with-stellate-cells-as-a-novel-3d-model-for-investigation-of%C3%A2-stroma-mediated-cell-motility-and-drug-resistance
#3
Ji-Hyun Lee, Seul-Ki Kim, Iftikhar Ali Khawar, Su-Yeong Jeong, Seok Chung, Hyo-Jeong Kuh
BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance...
January 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29328401/long-non-coding-rna-meg3-functions-as-a-tumour-suppressor-and-has-prognostic-predictive-value-in-human-pancreatic-cancer
#4
Ling Ma, Feng Wang, Chong Du, Zhengkui Zhang, Huahu Guo, Xuehai Xie, Hongqiao Gao, Yan Zhuang, Marko Kornmann, Hong Gao, Xiaodong Tian, Yinmo Yang
Long non-coding RNA (lncRNA) MEG3 has been demonstrated to be a tumour suppressor in many malignancies. However, the functional role of MEG3 in pancreatic cancer (PC) is unclear. In this study, the expression pattern of MEG3 was evaluated in 25 samples of microdissected PC tissues and 8 PC cell lines and was compared to the expression in adjacent non‑cancerous tissues and a human pancreatic normal epithelial cell line. Loss of MEG3 expression was observed in both the cancerous tissues and cancer cell lines...
January 2, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29315556/kras-promotes-tumor-metastasis-and-chemoresistance-by-repressing-rkip-via-the-mapk-erk-pathway-in-pancreatic-cancer
#5
Kege Yang, Yaqing Li, Guoda Lian, Haoming Lin, Changzhen Shang, Linjuan Zeng, Shaojie Chen, Jiajia Li, Chumei Huang, Kaihong Huang, Yinting Chen
Oncogenic KRAS plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. However, the mechanism has not been clearly elucidated. RKIP is a tumor repressor, and loss of RKIP has been shown in PDAC. Here, we found that KRAS expression was inversely correlated with RKIP expression in PDAC fresh tissue regardless of the KRAS mutant status. The negative correlation between KRAS and RKIP was further confirmed in our PDAC tissue microarray. KRAS overexpression and RKIP downregulation were associated with poor clinical outcomes...
January 8, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29274277/cul4b-promotes-metastasis-and-proliferation-in-pancreatic-cancer-cells-by-inducing-epithelial-mesenchymal-transition-via-the-wnt-%C3%AE-catenin-signaling-pathway
#6
Yue-Ming He, Yu-Sha Xiao, Lei Wei, Jia-Qiang Zhang, Cheng-Hong Peng
This study determines whether cullin 4B (CUL4B) promotes pancreatic cancer (PC) metastasis by inducing epithelial-mesenchymal transition (EMT) via the Wnt/β-catenin signaling pathway. Sixty-four PC patients were enrolled in this study. Human PC cell lines were distributed into blank, negative control, shCUL4B, PLOC, PLOC-CUL4B and PLOC-CUL4B + siRNA-β-catenin groups. The expressions of CUL4B, Wnt/β-catenin signaling pathway-related proteins, and EMT-related proteins were determined using RT-qPCR and western blotting...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29258566/5-fu-resistant-emt-like-pancreatic-cancer-cells-are-hypersensitive-to-photochemical-internalization-of-the-novel-endoglin-targeting-immunotoxin-cd105-saporin
#7
Kaja Lund, Cathrine Elisabeth Olsen, Judith Jing Wen Wong, Petter Angell Olsen, Nina Therese Solberg, Anders Høgset, Stefan Krauss, Pål Kristian Selbo
BACKGROUND: Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. METHODS: 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS2a and to investigate the effect of photodamage of lysosomes...
December 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29229918/negative-regulation-of-tgf-%C3%AE-1-induced-mkk6-p38-and-mek-erk-signalling-and-epithelial-mesenchymal-transition-by-rac1b
#8
David Witte, Hannah Otterbein, Maria Förster, Klaudia Giehl, Robert Zeiser, Hendrik Lehnert, Hendrik Ungefroren
Prompted by earlier findings that the Rac1-related isoform Rac1b inhibits transforming growth factor (TGF)-β1-induced canonical Smad signalling, we studied here whether Rac1b also impacts TGF-β1-dependent non-Smad signalling such as the MKK6-p38 and MEK-ERK mitogen-activated protein kinase (MAPK) pathways and epithelial-mesenchymal transition (EMT). Transient depletion of Rac1b protein in pancreatic cancer cells by RNA interference increased the extent and duration of TGF-β1-induced phosphorylation of p38 MAPK in a Smad4-independent manner...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222037/diabetes-as-risk-factor-for-pancreatic-cancer-hyperglycemia-promotes-epithelial-mesenchymal-transition-and-stem-cell-properties-in-pancreatic-ductal-epithelial-cells
#9
Sascha Rahn, Vivien Zimmermann, Fabrice Viol, Hendrike Knaack, Kerstin Stemmer, Lena Peters, Lennart Lenk, Hendrik Ungefroren, Dieter Saur, Heiner Schäfer, Ole Helm, Susanne Sebens
Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation...
February 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29215048/high-dose-parenteral-ascorbate-inhibited-pancreatic-cancer-growth-and-metastasis-mechanisms-and-a-phase-i-iia-study
#10
Kishore Polireddy, Ruochen Dong, Gregory Reed, Jun Yu, Ping Chen, Stephen Williamson, Pierre-Christian Violet, Ziyan Pessetto, Andrew K Godwin, Fang Fan, Mark Levine, Jeanne A Drisko, Qi Chen
Pancreatic cancer is among the most lethal cancers with poorly tolerated treatments. There is increasing interest in using high-dose intravenous ascorbate (IVC) in treating this disease partially because of its low toxicity. IVC bypasses bioavailability barriers of oral ingestion, provides pharmacological concentrations in tissues, and exhibits selective cytotoxic effects in cancer cells through peroxide formation. Here, we further revealed its anti-pancreatic cancer mechanisms and conducted a phase I/IIa study to investigate pharmacokinetic interaction between IVC and gemcitabine...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214772/pseudolaric-acid-b-inhibits-proliferation-invasion-and-epithelial-to-mesenchymal-transition-in-human-pancreatic-cancer-cell
#11
Xiaoyu Li, Xianzhi Zhao, Wen Song, Zibin Tian, Lin Yang, Qinghui Niu, Qi Zhang, Man Xie, Bin Zhou, Yonghong Xu, Jun Wu, Cuiping Zhang
PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules...
January 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29196101/mir-135b-5p-promotes-migration-invasion-and-emt-of-pancreatic-cancer-cells-by-targeting-nr3c2
#12
Zhengliang Zhang, Xiangming Che, Ni Yang, Zhenghai Bai, Yuan Wu, Li Zhao, Honghong Pei
The exact mechanisms of metastasis for pancreatic cancer remain to be uncovered. This study aimed to elucidate the potential functional mechanism of miR-135b-5p in migration, invasion and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells. By real-time PCR and analysis of GEO database, we determined the up-regulated expression of miR-135b-5p in pancreatic cancer tissues and cell lines. Clinically, highly expressed miR-135b-5p was closely related to advanced TNM stage, more lymph node metastasis, more distant metastasis and worse overall survival (OS) and disease-free survival (DFS)...
November 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29190794/3d-collagen-fibrillar-microstructure-guides-pancreatic-cancer-cell-phenotype-and-serves-as-a-critical-design-parameter-for-phenotypic-models-of-emt
#13
T J Puls, Xiaohong Tan, Catherine F Whittington, Sherry L Voytik-Harbin
Pancreatic cancer, one of the deadliest cancers, is characterized by high rates of metastasis and intense desmoplasia, both of which are associated with changes in fibrillar type I collagen composition and microstructure. Epithelial to mesenchymal transition (EMT), a critical step of metastasis, also involves a change in extracellular matrix (ECM) context as cells detach from basement membrane (BM) and engage interstitial matrix (IM). The objective of this work was to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to define how ECM composition and biophysical properties modulate pancreatic cancer EMT...
2017: PloS One
https://www.readbyqxmd.com/read/29180466/synthetic-lethality-of-parp-inhibitors-in-combination-with-myc-blockade-is-independent-of-brca-status-in-triple-negative-breast-cancer
#14
Jason Pw Carey, Cansu Karakas, Tuyen Bui, Xian Chen, Smruthi Vijayaraghavan, Yang Zhao, Jing Wang, Keith Mikule, Jennifer K Litton, Kelly K Hunt, Khandan Keyomarsi
PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients. Several of those patients exhibit intrinsic/acquired resistance mechanisms that limit efficacy of PARPi monotherapy. Here we show how the efficacy of PARPi in triple-negative breast cancers (TNBC) can be expanded by targeting MYC-induced oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification of the MYC gene is correlated with increased expression of the homologous DNA recombination enzyme RAD51 and tumors overexpressing both genes are associated with worse overall survival...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29171033/actin-cytoskeleton-remodeling-drives-epithelial-mesenchymal-transition-for-hepatoma-invasion-and-metastasis
#15
Jei-Ming Peng, Rabindranath Bera, Chih-Yung Chiou, Ming-Chin Yu, Tse-Chin Chen, Chia-Wei Chen, Tsung-Rui Wang, Wan-Ling Chiang, Yongkun Wei, Huamin Wang, Mien-Chie Hung, Sen-Yung Hsieh
High invasiveness is a hallmark of human hepatocellular carcinoma (HCC). Large tumors predict invasion and metastasis. Epithelial-mesenchymal transition (EMT) is crucial for cancer invasion and metastasis. However, the mechanisms whereby large tumors tend to undergo EMT remain unclear. We conducted a subgenome-wide screen and identified KLHL23 as an HCC invasion suppressor via inhibiting EMT. KLHL23 binds to actin and suppresses actin polymerization. KLHL23 silencing induced filopodium and lamellipodium formation...
November 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29168159/lox-1-is-a-poor-prognostic-indicator-and-induces-epithelial-mesenchymal-transition-and-metastasis-in-pancreatic-cancer-patients
#16
Jie Zhang, Lei Zhang, Can Li, Caiting Yang, Lili Li, Shushu Song, Hao Wu, Fenglin Liu, Lan Wang, Jianxin Gu
PURPOSE: Pancreatic cancer (PC) is an aggressive type of cancer that exhibits a rapid progression. Previously LOX-1, which is a type II trans-membrane glycoprotein that is expressed in endothelial cells, has been found to be involved in the development of several types of cancer. As yet, however, the expression of LOX-1 and its functional consequences in PC have not been documented. The present study was aimed at investigating the prognostic relevance of LOX-1 expression in PC patients and at resolving its role in PC metastasis...
November 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29156810/psc-derived-galectin-1-inducing-epithelial-mesenchymal-transition-of-pancreatic-ductal-adenocarcinoma-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#17
Dong Tang, Jingqiu Zhang, Zhongxu Yuan, Hongpeng Zhang, Yang Chong, Yuqin Huang, Jie Wang, Qingquan Xiong, Sen Wang, Qi Wu, Ying Tian, Yongdie Lu, Xiao Ge, Wenjing Shen, Daorong Wang
Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151594/adipocytes-sustain-pancreatic-cancer-progression-through-a-non-canonical-wnt-paracrine-network-inducing-ror2-nuclear-shuttling
#18
C Carbone, G Piro, N Gaianigo, F Ligorio, R Santoro, V Merz, F Simionato, C Zecchetto, G Falco, G Conti, P T Kamga, M Krampera, F Di Nicolantonio, L De Franceschi, A Scarpa, G Tortora, D Melisi
BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage, and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human Bone Marrow Stromal Cells (hBMSC) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),RESULTS:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPO(CM)) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSC(CM)) from two different healthy donors...
November 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29137308/microrna-23a-promotes-pancreatic-cancer-metastasis-by-targeting-epithelial-splicing-regulator-protein-1
#19
Guo Wu, Zhonghu Li, Peng Jiang, Xi Zhang, Yingqiang Xu, Kai Chen, Xiaowu Li
miR-23a plays vital roles in various cancer metastases. Here, we found that miR-23a expression was significantly up-regulated in pancreatic cancer tissues compared with adjacent normal tissues. miR-23a up-regulation was significantly associated with differentiated degree, lymphoid nodal status, tumor invasion and poor survival rate in pancreatic cancer patients. We also found that miR-23a expression was significantly up-regulated in lymph node metastatic tissues and in pancreatic cancer cells that underwent epithelial-mesenchymal transition (EMT)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136735/-bit1-mediates-the-malignant-behaviors-in-pancreatic-cancer-and-its-potential-clinical-significance
#20
S Huang, D Yuan, J C Guo, T P Zhang, Y P Zhao
Objective: To investigate the potential role of Bit1 in the pathogenesis of pancreatic ductal cancer cells(PDAC) and its potential clinical application value. Methods: Real-time PCR and Western blot were employed to detect the expression of Bit1 in six pancreatic cancer cells, then the tool cells were selected to further study the function of Bit1.PolyHEMA was used to monitor the suspended cell culture condition in vitro.The invasion and migration abilities of pancreatic cancer cells were detected through Transwell assay...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
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