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pancreatic cancer EMT

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https://www.readbyqxmd.com/read/28337746/thymidylate-synthase-is-functionally-associated-with-zeb1-and-contributes-to-the-epithelial-to-mesenchymal-transition-of-cancer-cells
#1
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
#2
Xuejun Xu, Zhiping Zhao, Sixiang 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
#3
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
#4
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
#5
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)...
February 8, 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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28212565/the-mir-675-5p-regulates-the-progression-and-development-of-pancreatic-cancer-via-the-ubqln1-zeb1-mir200-axis
#9
Jue Wang, Youli Zhang, Hong Wei, Xingxing Zhang, Yan Wu, Aihua Gong, Yu Xia, Wenbing Wang, Min Xu
Pancreatic cancer (PC) is a highly lethal disease due to extensive metastatic lesions. Accumulating evidence suggests that miR-675-5p plays different roles in metastasis through the regulation of epithelial to mesenchymal (EMT) and the mesenchymal to epithelial transitions (MET) in different cancers. ZEB1 promotes the EMT process by controlling the expression of E-cadherin and may have a reciprocal regulation with Ubiquilin1 (UBQLN1) and mir-200 family in cancer progression. In the present study, we showed that decreased expression of miR-675-5p is associated with the enhanced cell proliferation and survival of PC cells, while the increased expression of mir-675-5p shows the opposite one...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193222/phosphorylation-dependent-regulation-of-aldh1a1-by-aurora-kinase-a-insights-on-their-synergistic-relationship-in-pancreatic-cancer
#10
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Jacoba White, Kavita Shah
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, and tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT and CSC phenotypes are not fully understood, which has hindered the development of effective targeted therapies capable of improving treatment outcomes in patients with pancreatic cancer. RESULTS: We show a central role of Aurora kinase A (AURKA) in promoting EMT and CSC phenotypes via ALDH1A1, which was discovered as its direct substrate using an innovative chemical genetic screen...
February 13, 2017: BMC Biology
https://www.readbyqxmd.com/read/28179411/pancreatic-neuroendocrine-tumors-and-emt-behavior-are-driven-by-the-csc-marker-dclk1
#11
Yu Ikezono, Jun Akiba, Mitsuhiko Abe, Takafumi Yoshida, Fumitaka Wada, Toru Nakamura, Hideki Iwamoto, Atsutaka Masuda, Takahiko Sakaue, Hirohisa Yano, Takuji Torimura, Osamu Tsuruta, Hironori Koga
Doublecortin-like kinase 1 (DCLK1), a marker for intestinal and pancreatic cancer stem cells, is highly expressed in neuroblastomas. This study was conducted to assess DCLK1 expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in clinical tissue from multiple PNET patients, cells (BON1, QGP1, and CM), and tumor xenografts. Immunohistochemically, all PNET tissues highly and diffusely expressed DCLK1 as a full-length isoform, identical to that detected in primary liver NETs...
February 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28167680/aurora-a-twist1-axis-promotes-highly-aggressive-phenotypes-in-pancreatic-carcinoma
#12
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Max Jacobsen, George Sandusky, Kavita Shah
We uncovered a crucial role of Aurora kinase A (AURKA)-Twist1 axis in promoting epithelial-to-mesenchymal transition (EMT) and chemoresistance in pancreatic cancer. Twist1 is the first EMT-specific target of AURKA that was identified using an innovative screen. AURKA phosphorylates Twist1 at three sites, which results in its multifaceted regulation- AURKA inhibits its ubiquitylation, increases transcriptional activity, and favors homodimerization. Twist1 reciprocates and prevents AURKA degradation, thereby triggering a feedback loop...
February 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28155598/development-of-in-vitro-co-culture-model-in-anti-cancer-drug-development-cascade
#13
Ruiling Xu, Frances M. Richards
Tumour microenvironment is recognized as a major determinant of intrinsic resistance to anticancer therapies. In solid tumour types, such as breast cancer, lung cancer and pancreatic cancer, stromal components provide a fibrotic niche, which promotes stemness, EMT, chemo- and radio-resistance of tumour. However, this microenvironment is not recapitulated in the conventional cell monoculture or xenografts, hence these in vitro and in vivo preclinical models are unlikely to be predictive of clinical response; which might attribute to the poor predictivity of these preclinical drug-screening models...
February 1, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28145431/mir-34a-inhibits-pancreatic-cancer-progression-through-snail1-mediated-epithelial-mesenchymal-transition-and-the-notch-signaling-pathway
#14
Yan Tang, Yong Tang, Ying-Sheng Cheng
Epithelial-mesenchymal transition (EMT) and Notch signaling are important for the growth and invasion of pancreatic cancer, which is a leading cause of cancer-related deaths worldwide. miR-34a has been shown to play pivotal roles in the progression of several types of cancer. However, little is known about the regulatory mechanisms of miR-34a in pancreatic cancer processes. The aim of this study was to determine whether miR-34a has negative effects on pancreatic cancer and whether these effects are related to EMT and Notch signaling...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144398/epithelial-mesenchymal-transition-as-a-therapeutic-target-for-overcoming-chemoresistance-in-pancreatic-cancer
#15
REVIEW
Omar Elaskalani, Norbaini Binti Abdol Razak, Marco Falasca, Pat Metharom
Pancreatic cancer has one of the worst prognoses among all cancers due to the late manifestation of identifiable symptoms and high resistance to chemo- and radiation therapies. In recent years, a cancer development phase termed epithelial-mesenchymal transition (EMT) has gained increasing research focus. The process is implicated in tumour metastasis, and emerging evidence suggests EMT also contributes or induces chemoresistance in several cancers. Nevertheless, the applicability of therapeutic targeting of EMT faces many challenges...
January 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28123853/curcumin-suppresses-epithelial-to-mesenchymal-transition-and-metastasis-of-pancreatic-cancer-cells-by-inhibiting-cancer-associated-fibroblasts
#16
Qing Wang, Chao Qu, Fang Xie, Lianyu Chen, Luming Liu, Xiaohua Liang, Xueyong Wu, Peng Wang, Zhiqiang Meng
Pancreatic cancer is one of the most lethal malignancies and the fourth leading cause of cancer-related deaths worldwide, because of its aggressive and highly metastatic ability even in its early stages. Cancer-associated fibroblasts (CAFs) have been reported to be vital to pancreatic cancer progression via regulating tumorigenesis and metastasis. Studies have shown that CAFs also mediate epithelial-to-mesenchymal transition (EMT) in tumor cells. Curcumin has recently been reported to have anticancer effects by modulating pathways involved in cancer progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28077929/hnrnpa2b1-regulates-the-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-through-the-erk-snail-signalling-pathway
#17
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
#18
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 this study, we demonstrated that the expression of miR-142 could be significantly suppressed in pancreatic cancer specimens and cell lines compared 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 a luciferase reporter experiment confirmed this discovery...
February 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28064441/analysis-of-the-origin-of-anaplastic-pancreatic-cancer-and-the-mechanism-of-its-dedifferentiation
#19
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, ZEB1, Snail, N-cadherin, CD24 and CD44 was estimated using immunohistochemistry. RESULTS: Almost all cases were positive for SOX9 expression...
March 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
#20
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
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