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pancreatic cancer EMT

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https://www.readbyqxmd.com/read/28444967/co-delivery-of-microrna-21-antisense-oligonucleotides-and-gemcitabine-using-nanomedicine-for-pancreatic-cancer-therapy
#1
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28414315/the-emt-activator-zeb1-is-a-key-factor-for-cell-plasticity-and-promotes-metastasis-in-pancreatic-cancer
#2
Angela M Krebs, Julia Mitschke, María Lasierra Losada, Otto Schmalhofer, Melanie Boerries, Hauke Busch, Martin Boettcher, Dimitrios Mougiakakos, Wilfried Reichardt, Peter Bronsert, Valerie G Brunton, Christian Pilarsky, Thomas H Winkler, Simone Brabletz, Marc P Stemmler, Thomas Brabletz
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28400334/asporin-promotes-pancreatic-cancer-cell-invasion-and-migration-by-regulating-the-epithelial-to-mesenchymal-transition-emt-through-both-autocrine-and-paracrine-mechanisms
#3
Lili Wang, Huanwen Wu, Li Wang, Hui Zhang, Junliang Lu, Zhiyong Liang, Tonghua Liu
Pancreatic cancer is histopathologically characterized by excessive desmoplasia induced by pancreatic stellate cells (PSCs). Asporin, an extracellular matrix (ECM) protein, is highly expressed in cancer-associated fibroblasts (CAFs). Asporin expression in PSCs and its roles in PSC-pancreatic cancer cell (PCC) interaction remain unclear. The present study firstly showed that Asporin is highly expressed in activated PSCs and is involved in PSC-mediated invasion and migration of PCCs. Exogenous Asporin interacted with the transmembrane receptor CD44 on PCCs to activate NF-κB/p65 and promoted the epithelial-mesenchymal transition (EMT) in PCCs...
April 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28396463/blind-selex-approach-identifies-rna-aptamer-that-regulate-emt-and-inhibit-metastasis
#4
Sorah Yoon, Brian Armstrong, Nagy Habib, John J Rossi
Identifying targets that are exposed on the plasma membrane of tumor cells, but expressed internally in normal cells, is a fundamental issue for improving the specificity and efficacy of anticancer therpeutics. Using blind cell SELEX (Systemic Evolution of Ligands by EXponetial enrichment) which is untargeted SELEX, we have identified an aptamer, P15, which specifically bound to the human pancreatic adenocarcinoma cells. To identify the aptamer binding plasma membrane protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used...
April 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28390160/the-role-of-small-gtpases-of-the-rho-rac-family-in-tgf-%C3%AE-induced-emt-and-cell-motility-in-cancer
#5
REVIEW
Hendrik Ungefroren, David Witte, Hendrik Lehnert
BACKGROUND: This article focusses on the role of Rho family GTPases and particularly Rac1 and Rac1b in TGF-β-induced epithelial-mesenchymal transition (EMT) and EMT-associated responses such as cell migration, invasion, and metastasis in cancer. RESULTS: EMT is considered a prerequisite for cells to adopt a motile and invasive phenotype and eventually become metastatic. A major regulator of EMT and metastasis in cancer is TGF-β and its specific functions on tumor cells are mediated besides Smad proteins and mitogen-activated protein kinases (MAPKs) by small GTPases of the Rho/Rac1 family...
April 8, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28388884/inhibition-of-six1-affects-tumour-invasion-and-the-expression-of-cancer-stem-cell-markers-in-pancreatic-cancer
#6
Tristan Lerbs, Savita Bisht, Sebastian Schölch, Mathieu Pecqueux, Glen Kristiansen, Martin Schneider, Bianca T Hofmann, Thilo Welsch, Christoph Reissfelder, Nuh N Rahbari, Johannes Fritzmann, Peter Brossart, Jürgen Weitz, Georg Feldmann, Christoph Kahlert
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSC) contribute to tumour progression and metastasis. Assessment of transcription factors involved in these two mechanisms can help to identify new targets for an oncological therapy. In this study, we focused on the evaluation of the transcription factor Six1 (Sine oculis 1). This protein is involved in embryologic development and its contribution to carcinogenesis has been described in several studies. METHODS: Immunohistochemistry against Six1 was performed on a tissue microarray containing specimens of primary pancreatic ductal adenocarcinomas (PDAC) of 139 patients...
April 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28388562/cbx7-negatively-regulates-migration-and-invasion-in-glioma-via-wnt-%C3%AE-catenin-pathway-inactivation
#7
Zhongyuan Bao, Xiupeng Xu, Yinlong Liu, Honglu Chao, Chao Lin, Zheng Li, Yongping You, Ning Liu, Jing Ji
CBX7, a member of the Polycomb-group proteins, plays a significant role in normal and cancerous tissues and has been defined as a tumor suppressor in thyroid, breast and pancreatic cancers. However, its function in glioma remains undefined. CBX7 expression is decreased in glioma, especially in higher grade cases, according to data in the CGGA, GSE16001 and TCGA databases. Further experimental evidence has shown that exogenous CBX7 overexpression induced apoptosis and inhibited cell proliferation, colony formation and migration of glioma cells...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373289/mir-202-diminishes-tgfbeta-receptors-and-attenuates-tgfbeta1-induced-emt-in-pancreatic-cancer
#8
Hardik Mody, Sau Wai Hung, Rakesh Pathak, Jazmine Griffin, Zobeida Cruz-Monserrate, Rajgopal Govindarajan
Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs (miRs) to regulate endogenous TGFbeta1 levels via miR-663/4787 mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). While DZNep also attenuates exogenous TGFbeta-induced EMT response, the mechanism of this inhibition was unclear...
April 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28369619/histone-deacetylase-class-i-inhibition-promotes-epithelial-gene-expression-in-pancreatic-cancer-cells-in-a-brd4-and-myc-dependent-manner
#9
Vivek Kumar Mishra, Florian Wegwitz, Robyn Laura Kosinsky, Madhobi Sen, Roland Baumgartner, Tanja Wulff, Jens T Siveke, Hans-Ulrich Schildhaus, Zeynab Najafova, Vijayalakshmi Kari, Hella Kohlhof, Elisabeth Hessmann, Steven A Johnsen
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity is frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role in PDAC. In this study, we investigated the effects of the class I-specific HDAC inhibitor (HDACi) 4SC-202 in multiple PDAC cell lines in promoting tumor cell differentiation. We show that 4SC-202 negatively affects TGFβ signaling and inhibits TGFβ-induced epithelial-to-mesenchymal transition (EMT)...
March 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28368414/tgf%C3%AE-engages-mek-erk-to-differentially-regulate-benign-and-malignant-pancreas-cell-function
#10
D R Principe, A M Diaz, C Torres, R J Mangan, B DeCant, R McKinney, M-S Tsao, A Lowy, H G Munshi, B Jung, P J Grippo
While TGFβ signals are anti-proliferative in benign and well-differentiated pancreatic cells, TGFβ appears to promote the progression of advanced cancers. To better understand dysregulation of the TGFβ pathway, we first generated mouse models of neoplastic disease with TGFβ receptor deficiencies. These models displayed reduced levels of pERK irrespective of KRAS mutation. Furthermore, exogenous TGFβ led to rapid and sustained TGFBR1-dependent ERK phosphorylation in benign pancreatic duct cells. Similar to results that our group has published in colon cancer cells, inhibition of ERK phosphorylation in duct cells mitigated TGFβ-induced upregulation of growth suppressive pSMAD2 and p21, prevented downregulation of the pro-growth signal CDK2 and ablated TGFβ-induced EMT...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28355965/long-noncoding-rna-pvt1-promotes-emt-and-cell-proliferation-and-migration-through-downregulating-p21-in-pancreatic-cancer-cells
#11
Bao-Qiang Wu, Yong Jiang, Feng Zhu, Dong-Lin Sun, Xiao-Zhou He
BACKGROUND AND AIM: Long noncoding RNA-plasmacytoma variant translocation 1 is identified to be highly expressed and exhibits oncogenic activity in a variety of human malignancies, including pancreatic cancer. However, little is known about the overall biological role and mechanism of plasmacytoma variant translocation 1 in pancreatic cancer so far. In this study, we investigated the effect of plasmacytoma variant translocation 1 on pancreatic cancer cell proliferation and migration as well as epithelial-mesenchymal transition...
January 1, 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/28344092/the-over-expression-of-long-non-coding-rna-anril-promotes-epithelial-mesenchymal-transition-by-activating-the-atm-e2f1-signaling-pathway-in-pancreatic-cancer-an-in-vivo-and-in-vitro-study
#12
Shi Chen, Jia-Qiang Zhang, Jiang-Zhi Chen, Hui-Xing Chen, Fu-Nan Qiu, Mao-Lin Yan, Yan-Ling Chen, Cheng-Hong Peng, Yi-Feng Tian, Yao-Dong Wang
This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway...
March 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28337746/thymidylate-synthase-is-functionally-associated-with-zeb1-and-contributes-to-the-epithelial-to-mesenchymal-transition-of-cancer-cells
#13
Aarif Siddiqui, Maria Eleni Vazakidou, Annemarie Schwab, Francesca Napoli, Cristina Fernandez-Molina, Ida Rapa, Marc P Stemmler, Marco Volante, Thomas Brabletz, Paolo Ceppi
Thymidylate synthase (TS) is a fundamental enzyme of nucleotide metabolism and one of the oldest anti-cancer targets. Beginning from the analysis of gene array data from the NCI-60 panel of cancer cell lines, we identified a significant correlation at both gene and protein level between TS and the markers of epithelial-to-mesenchymal transition (EMT), a developmental process that allows cancer cells to acquire features of aggressiveness, like motility and chemoresistance. TS levels were found to be significantly augmented in mesenchymal-like compared to epithelial-like cancer cells, to be regulated by EMT induction, and to negatively correlate with micro-RNAs (miRNAs) usually expressed in epithelial-like cells and known to actively suppress EMT...
March 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28315433/increased-semaphorin-3c-expression-promotes-tumor-growth-and-metastasis-in-pancreatic-ductal-adenocarcinoma-by-activating-the-erk1-2-signaling-pathway
#14
Xuejun Xu, Zhiping Zhao, Shixiang Guo, Jian Li, Songsong Liu, Yu You, Bing Ni, Huaizhi Wang, Ping Bie
Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28281184/tgf-%C3%AE-1-mir-200a-pten-induces-epithelial-mesenchymal-transition-and-fibrosis-of-pancreatic-stellate-cells
#15
Min Xu, Guoying Wang, Hailang Zhou, Jing Cai, Ping Li, Meng Zhou, Ying Lu, Xiaomeng Jiang, Hongmei Huang, Youli Zhang, Aihua Gong
Although the function of miR-200a has been discussed in many cancers and fibrotic diseases, its role in pancreatic fibrosis is still poorly understood. In this study, we for the first time confirm that miR-200a attenuates TGF-β1-induced pancreatic stellate cells activation and extracellular matrix formation. First, we find that TGF-β1 induces activation and extracellular matrix (ECM) formation in PSCs, and the effects are blocked by the inhibitor of PI3K (LY294002). Furthermore, we identify that miR-200a is down-regulated in TGF-β1-activated PSCs, and up-regulation of miR-200a inhibits PSCs activation induced by TGF-β1...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28259973/furin-promotes-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-via-hippo-yap-pathway
#16
Youli Zhang, Meng Zhou, Hong Wei, Hailang Zhou, Junbo He, Ying Lu, Dawei Wang, Baoding Chen, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong, Min Xu
Furin, a well-characterized proprotein convertase, plays an important role in many diseases and links to tumor metastasis. However, the role of furin in pancreatic cancer progression remains to be elucidated. In the present study, we found that furin promotes the growth and the epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. First, we found that furin knockdown significantly inhibited proliferation, invasion and migration in BxPC3 and SW1990 cells, while furin overexpression promoted the above behavior in PANC1 and PaTu8988 cells...
March 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28259943/sclareolide-enhances-gemcitabine%C3%A2-induced-cell-death-through-mediating-the-nicd-and-gli1-pathways-in-gemcitabine%C3%A2-resistant-human-pancreatic-cancer
#17
Sheng Chen, Ye Wang, Wen-Long Zhang, Mao-Sheng Dong, Jian-Hua Zhang
Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs)...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28245823/the-epithelial-to-mesenchymal-transition-emt-and-cancer-stem-cells-implication-for-treatment-resistance-in-pancreatic-cancer
#18
REVIEW
Pingting Zhou, Bo Li, Furao Liu, Meichao Zhang, Qian Wang, Yuanhua Liu, Yuan Yao, Dong Li
The mechanical properties of epithelial to mesenchymal transition (EMT) and a pancreatic cancer subpopulation with stem cell properties have been increasingly recognized as potent modulators of the effective of therapy. In particular, pancreatic cancer stem cells (PCSCs) are functionally important during tumor relapse and therapy resistance. In this review we have surveyed recent advances in the role of EMT and PCSCs in tumor progression, metastasis and treatment resistance, and the mechanisms of integrated with biochemical signals and the underlying pathways involved in treatment resistance of pancreatic cancer...
February 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28244691/up-regulation-of-glycolysis-promotes-the-stemness-and-emt-phenotypes-in-gemcitabine-resistant-pancreatic-cancer-cells
#19
Hengqiang Zhao, Qingke Duan, Zhengle Zhang, Hehe Li, Heshui Wu, Qiang Shen, Chunyou Wang, Tao Yin
Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT)-type cells are considered as underlying causes of chemoresistance, tumour recurrence and metastasis in pancreatic cancer. We aimed to describe the mechanisms - particularly glycolysis - involved in the regulation of the CSC and EMT phenotypes. We used a gemcitabine-resistant (GR) Patu8988 cell line, which exhibited clear CSC and EMT phenotypes and showed reliance on glycolysis. Inhibition of glycolysis using 2-deoxy-D-glucose (2-DG) significantly enhanced the cytotoxicity of gemcitabine and inhibited the CSC and EMT phenotypes in GR cells both in vitro and in vivo...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28217707/microrna-regulation-of-human-pancreatic-cancer-stem-cells
#20
REVIEW
Yi-Fan Xu, Bethany N Hannafon, Wei-Qun Ding
microRNAs (miRNAs) are a group of small non-coding RNAs that function primarily in the post transcriptional regulation of gene expression in plants and animals. Deregulation of miRNA expression in cancer cells, including pancreatic cancer cells, is well documented, and the involvement of miRNAs in orchestrating tumor genesis and cancer progression has been recognized. This review focuses on recent reports demonstrating that miRNAs are involved in regulation of pancreatic cancer stem cells (CSCs). A number of miRNA species have been identified to be involved in regulating pancreatic CSCs, including miR-21, miR-34, miR-1246, miR-221, the miR-17-92 cluster, the miR-200 and let-7 families...
2017: Stem Cell Investigation
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