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pancreatic cancer EMT

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https://www.readbyqxmd.com/read/28077929/hnrnpa2b1-regulates-the-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-through-the-erk-snail-signalling-pathway
#1
Shengjie Dai, Jie Zhang, Shihao Huang, Bin Lou, Binbo Fang, Tingting Ye, Xince Huang, Bicheng Chen, Mengtao Zhou
BACKGROUND: Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is closely related to tumour occurrence and development, oncogene expression, apoptosis inhibition and invasion and metastasis capacities. However, its function in the epithelial-mesenchymal transition (EMT) of pancreatic cancer is not fully understood. METHODS: By comparing various wild-type pancreatic cancer cell lines, we determined which have a higher expression level of HNRNPA2B1 accompanied by the higher expression of N-cadherin and vimentin and lower expression of E-cadherin...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28069592/mir-142-modulates-human-pancreatic-cancer-proliferation-and-invasion-by-targeting-hypoxia-inducible-factor-1-hif-1%C3%AE-in-the-tumor-microenvironments
#2
Yebin Lu, Niandong Ji, Wei Wei, Weijia Sun, Xuejun Gong, Xitao Wang
MicroRNAs regulate most protein-coding genes, including genes important in cancer and other diseases. In our study, we demonstrated that the expression of miR-142 could be significantly suppressed in pancreatic cancer specimens and cell lines, comparing to their adjacent tissues and normal pancreatic cells. Growth and invasion of PANC-1 and SW1990 cells were attenuated by overexpression of miR-142 in vitro With the help of bioinformatics analysis, hypoxia-inducible factor 1 (HIF-1α) was identified to be a direct target of miR-142, and luciferase reporter experiment confirmed this discovery...
January 9, 2017: Biology Open
https://www.readbyqxmd.com/read/28064441/analysis-of-the-origin-of-anaplastic-pancreatic-cancer-and-the-mechanism-of-its-dedifferentiation
#3
Kotaro Miura, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Go Ohira, Kohei Nishio, Naoki Kametani, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: We researched the origin and progression of anaplastic pancreatic cancer (APC) from the viewpoints of cell lineage, epithelial-mesenchymal transition (EMT) and cancer stem like cells (CSC). METHODS: Using specimens from patients with APC and differentiated pancreatic ductal adenocarcinoma (PDAC), expression of sex-determining region Y box 9 (SOX9), E-cadherin, vimentin, ZEB-1, Snail, N-cadherin, CD24 and CD44 was estimated using immunohistochemistry...
January 8, 2017: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28064436/mir-181b-5p-ets1-and-c-met-pathway-exacerbates-the-prognosis-of-pancreatic-ductal-adenocarcinoma-after-radiation-therapy
#4
Hideo Tomihara, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Takehiro Noda, Tadafumi Asaoka, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens exhibited remnant tumor cells, which indicated that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the epithelial-mesenchymal transition (EMT) and the presence of cancer stem cells (CSCs) were reported to be associated with resistance in various cancers...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28053127/potent-emt-and-csc-phenotypes-are-induced-by-oncostatin-m-in-pancreatic-cancer
#5
Jacob M Smigiel, Neetha Parameswaran, Mark W Jackson
: Pancreatic ductal adenocarcinoma (PDAC) is referred to as a silent killer due to the lack of clear symptoms, a lack of early detection methods, and a high frequency of metastasis at diagnosis. In addition, pancreatic cancer is remarkably resistant to chemotherapy, and clinical treatment options remain limited. The tumor microenvironment (TME) and associated factors are important determinants of metastatic capacity and drug resistance. Here, oncostatin M (OSM), an IL-6 cytokine family member, was identified as an important driver of mesenchymal and cancer stem cell (CSC) phenotypes...
January 4, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27996162/effect-of-nr5a2-inhibition-on-pancreatic-cancer-stem-cell-csc-properties-and-epithelial-mesenchymal-transition-emt-markers
#6
Zhaofan Luo, Yanan Li, Zuo Mingxin, Chang Liu, Dong Yan, Huamin Wang, Donghui Li
NR5A2 (aka LRH-1) has been identified as a pancreatic cancer susceptibility gene with missing biological link. This study aims to demonstrate expression and potential role of NR5A2 in pancreatic cancer. NR5A2 expression was quantified in resected pancreatic ductal adenocarcinomas and the normal adjacent tissues of 134 patients by immunohistochemistry. The intensity and extent of NR5A2 staining was quantified and analyzed in association with overall survival (OS). The impact of NR5A2 knockdown on pancreatic cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) markers was examined in cancer cells using RT-PCR and Western Blot...
December 20, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27990211/automated-electrorotation-shows-electrokinetic-separation-of-pancreatic-cancer-cells-is-robust-to-acquired-chemotherapy-resistance-serum-starvation-and-emt
#7
Timothy Lannin, Wey-Wey Su, Conor Gruber, Ian Cardle, Chao Huang, Fredrik Thege, Brian Kirby
We used automated electrorotation to measure the cytoplasmic permittivity, cytoplasmic conductivity, and specific membrane capacitance of pancreatic cancer cells under environmental perturbation to evaluate the effects of serum starvation, epithelial-to-mesenchymal transition, and evolution of chemotherapy resistance which may be associated with the development and dissemination of cancer. First, we compared gemcitabine-resistant BxPC3 subclones with gemcitabine-naive parental cells. Second, we serum-starved BxPC3 and PANC-1 cells and compared them to untreated counterparts...
November 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27987431/acriflavine-inhibits-acquired-drug-resistance-by-blocking-the-epithelial-to-mesenchymal-transition-and-the-unfolded-protein-response
#8
Jeroen Dekervel, Ashenafi Bulle, Petra Windmolders, Diether Lambrechts, Eric Van Cutsem, Chris Verslype, Jos van Pelt
: Epithelial-to-mesenchymal transition (EMT) is linked to tumor invasion, drug resistance and aggressive disease and this is largely dependent on the cell's microenvironment. Acriflavine (ACF) is an old antibacterial drug recently also suggested as anticancer agent and HIF inhibitor. We wanted to study the effect of acriflavine on EMT in different human cancer models. Pancreatic cancer cells (Panc-1) were exposed to TGF-β1 or cobalt chloride (to mimick severe hypoxia) to induce EMT. For our third model we exposed HepG2 liver cancer cells to sorafenib which resulted in development of acquired drug resistance with strong features of EMT and aggressive behavior...
December 14, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27983920/cdgsh-iron-sulfur-domain-2-activates-proliferation-and-emt-of-pancreatic-cancer-cells-via-wnt-%C3%AE-catenin-pathway-and-has-prognostic-value-in-human-pancreatic-cancer
#9
Yang Yang, Yuan-Song Bai, Qing Wang
Recently, increasing evidence has shown that CDGSH iron sulfur domain2 (CISD2) is involved in the initiation and metastasis of several cancers. However, the evidence of its potential role in pancreatic cancer is still lacking. In our present study, CISD2 was found to be increased in pancreatic cancer samples and multiple cell lines. Moreover, statistical analysis revealed that a high level of CISD2 was related to advanced clinical stage, advanced T-stage, positive vascular invasion, positive distant metastasis, and larger tumor size...
October 26, 2016: Oncology Research
https://www.readbyqxmd.com/read/27974798/mechanism-of-early-dissemination-and-metastasis-in-her2-mammary-cancer
#10
Kathryn L Harper, Maria Soledad Sosa, David Entenberg, Hedayatollah Hosseini, Julie F Cheung, Rita Nobre, Alvaro Avivar-Valderas, Chandandaneep Nagi, Nomeda Girnius, Roger J Davis, Eduardo F Farias, John Condeelis, Christoph A Klein, Julio A Aguirre-Ghiso
Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant. Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours. However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases. These findings, and those in pancreatic cancer and melanoma models, indicate that dissemination might occur during the early stages of tumour evolution...
December 14, 2016: Nature
https://www.readbyqxmd.com/read/27936345/targeting-integrin-linked-kinase-to-suppress-oncogenic-kras-signaling-in-pancreatic-cancer
#11
Po-Chen Chu, Samuel K Kulp, Tanios Bekaii-Saab, Ching-Shih Chen
Although oncogenic KRAS represents a therapeutically relevant target in pancreatic cancer, it is deemed "non-druggable" because of the intrinsic difficulty in designing direct inhibitors of KRAS. Our recent work demonstrated a KRAS-integrin-linked kinase (ILK) regulatory feedback loop that allows pancreatic cancer cells to regulate KRAS expression and to interact with the tumor microenvironment to promote aggressive phenotype. KRAS induces E2F1-mediated transcriptional activation of ILK expression, and ILK, in turn, controls KRAS expression via hnRNPA1, which binds and destabilizes the G-quadruplex in the KRAS promoter...
December 9, 2016: Small GTPases
https://www.readbyqxmd.com/read/27914516/leukotriene-b4-induces-emt-and-vimentin-expression-in-panc-1-pancreatic-cancer-cells-involvement-of-blt2-via-erk2-activation
#12
You Ri Kim, Mi Kyung Park, Gyeong Jin Kang, Hyun Ji Kim, Eun Ji Kim, Hyun Jung Byun, Moo-Yeol Lee, Chang Hoon Lee
Leukotriene B4 (LTB4) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB4 is known to be correlated with cancer progression. LTB4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR...
December 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27898661/methyl-cpg-binding-domain-3-inhibits-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-via-tgf-%C3%AE-smad-signalling
#13
Min Xu, Junbo He, Jie Li, Wen Feng, Hailang Zhou, Hong Wei, Meng Zhou, Ying Lu, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong
BACKGROUND: Methyl-CpG-binding domain 3 (MBD3) is an aberrant expression in human malignancies. However, the role of MBD3 in pancreatic cancer progression remains to be clarified. In this study, we investigated the effects of MBD3 on the epithelial-mesenchymal transition (EMT), and the underlying mechanism in pancreatic cancer cells. METHODS: The abilities of migration and invasion were examined by transwell and BD Matrigel invasion assays. EMT and TGF-β/Smad signalling were evaluated...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27893715/tgf%C3%AE-promotes-mesenchymal-phenotype-of-pancreatic-cancer-cells-in-part-through-epigenetic-activation-of-vav1
#14
P-H Huang, P-J Lu, L-Y Ding, P-C Chu, W-Y Hsu, C-S Chen, C-C Tsao, B-H Chen, C-T Lee, Y-S Shan, C-S Chen
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889393/triple-amirna-vegfrs-inhibition-in-pancreatic-cancer-improves-the-efficacy-of-chemotherapy-through-emt-regulation
#15
Jianfei Huang, Haijun Mei, Zhiyuan Tang, Jieying Li, Xiaojing Zhang, Yixiang Lu, Fang Huang, Qin Jin, Zhiwei Wang
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal outcome. Both novel prognostic markers and therapeutic targets are needed to improve the overall outcome of patients. Although single or double VEGFRs have been studied in PDAC, little is known about the role of triple combination of VEGFRs (VEGFR1, 2, and 3) in prognosis and therapy. We determined VEGFRs protein expression in 241 pancreatic tissues by tissue microarray immunohistochemistry (TMA-IHC), and correlated with patients' clinical characteristics and overall survival...
November 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27878247/oridonin-inhibition-and-mir%C3%A2-200b%C3%A2-3p-zeb1-axis-in-human-pancreatic-cancer
#16
Zhifang Gui, Feng Luo, Yayang Yang, Can Shen, Shuquan Li, Jian Xu
The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27878234/prometastatic-mechanisms-of-caf-mediated-emt-regulation-in-pancreatic-cancer-cells
#17
Tao Shan, Shuo Chen, Xi Chen, Wan Run Lin, Wei Li, Jiancang Ma, Tao Wu, Hong Ji, Yiming Li, Xijuan Cui, Ya'an Kang
Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27825542/histopathological-tumor-invasion-of-the-mesenterico-portal-vein-is-characterized-by-aggressive-biology-and-stromal-fibroblast-activation
#18
Hryhoriy Lapshyn, Louisa Bolm, Ilona Kohler, Martin Werner, Franck G Billmann, Dirk Bausch, Ulrich T Hopt, Frank Makowiec, Uwe A Wittel, Tobias Keck, Peter Bronsert, Ulrich F Wellner
BACKGROUND: Mesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology. METHODS: Patients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database...
November 5, 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/27822411/radiation-promotes-epithelial-to-mesenchymal-transition-and-invasion-of-pancreatic-cancer-cell-by-activating-carcinoma-associated-fibroblasts
#19
Doudou Li, Chao Qu, Zhouyu Ning, Haiyong Wang, Kun Zang, Liping Zhuang, Lianyu Chen, Peng Wang, Zhiqiang Meng
The tumor microenvironment is of crucial importance affecting treatment and prognosis. High degree of carcinoma-associated fibroblast (CAF) infiltration occurs in pancreatic cancer, though its effect on radiotherapy remains unclear. In this study, we demonstrated that radiation enhanced the migration- and invasion-promoting capacity of CAFs both in vitro and in vivo in a lung metastasis model. Radiation exposure increased the expression of CXCL12 by CAFs. CAF-derived CXCL12 promoted tumor cell EMT and invasion directly, acting through CXCR4 on pancreatic cancer cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27795830/advance-in-microrna-as-a-potential-biomarker-for-early-detection-of-pancreatic-cancer
#20
REVIEW
Jing Huang, Jianzhou Liu, Kevin Chen-Xiao, Xuemei Zhang, W N Paul Lee, Vay Liang W Go, Gary Guishan Xiao
Pancreatic cancer is characterized as a disease with low survival and high mortality because of no effective diagnostic and therapeutic strategies available in clinic. Conventional clinical diagnostic methods including serum markers and radiological imaging (CT, MRI, EUS, etc.) often fail to detect precancerous or early stage lesions. Development of effective biomarkers is unmet for reduction of mortality of pancreatic cancer. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs playing roles in regulation of cell physiology including tumorigenesis, apoptotic escape, proliferation, invasion, epithelial-mesenchymal transition (EMT), metastasis and chemoresistance...
2016: Biomarker Research
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