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pancreatic cancer EMT

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https://www.readbyqxmd.com/read/29775598/selective-cytotoxicity-of-the-nampt-inhibitor-fk866-toward-gastric-cancer-cells-with-markers-of-the-epithelial-mesenchymal-transition-due-to-loss-of-naprt
#1
Jooyoung Lee, Hyosil Kim, Jae Eun Lee, Su-Jin Shin, Sejin Oh, Sungjin Kwon, Hakhyun Kim, Yoon Young Choi, Michael A White, Soonmyung Paik, Jae-Ho Cheong, Hyun Seok Kim
BACKGROUND & AIMS: Markers of the epithelial-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor outcomes of patients. We performed a screen to identify pharmacologic compounds that kill gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms. METHODS: We identified 29 gastric cancer cell lines with gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed their mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based in invasive activity and protein markers...
May 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29760585/mir-93-5p-enhance-lacrimal-gland-adenoid-cystic-carcinoma-cell-tumorigenesis-by-targeting-brms1l
#2
Jie Hao, Xin Jin, Yan Shi, Hong Zhang
Background: Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignancies that affects lacrimal gland. MicroRNAs are known to play a crucial role as oncogenes or tumor suppressors. Specifically, miR-93 has been reported to play a crucial role in colorectal, breast, pancreatic, lung cancer and hepatocellular carcinoma. However, the role of miR-93 in LACC and the potential molecular mechanisms involved remain unknown. Therefore, we took the challenge to determine the involvement of miR-93 in the LACC by targeting BRMS1L...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29758199/pafah1b2-is-a-hif1a-target-gene-and-promotes-metastasis-in-pancreatic-cancer
#3
Can Ma, Yan Guo, Yan Zhang, Aixia Duo, Yitao Jia, Ci Liu, Binghui Li
Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial-mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes...
May 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29749486/effects-of-obatoclax-combined-with-gemcitabine-on-the-biological-activity-of-pancreatic-cancer-cells-under-hypoxic-conditions
#4
Xin-Fang Hou, Shuai Li, Chen Wu, Ke Li, Shu-Ning Xu, Ju-Feng Wang
The present study aimed to investigate the effects of obatoclax (OBX) combined with gemcitabine (GEM) treatment on the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) related proteins of pancreatic cancer cell line BxPC‑3 under hypoxic conditions. Protein expression levels of hypoxia‑inducible factor 1α (HIF‑1α) in BxPC‑3 pancreatic cancer cells under normoxic and hypoxic conditions were detected by western blotting. Cells were divided into four groups: Normoxia group, hypoxia group, OBX group and OBX + GEM group...
April 26, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29749431/expression-of-annexin-ii-and-stromal-tenascin-c-promotes-epithelial-to-mesenchymal-transition-and-correlates-with-distant-metastasis-in-pancreatic-cancer
#5
Naoko Yoneura, Shigetsugu Takano, Hideyuki Yoshitomi, Yasuyuki Nakata, Reiri Shimazaki, Shingo Kagawa, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka
The interaction between cancer cells and stromal components contributes to cancer invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). The present study investigated the role of the correlation between annexin II (ANX2) and stromal tenascin C (TNC) with the progression of PDAC. The functions of the expression ANX2 and TNC were assessed in in vitro experiments using mouse and human PDAC cells, and the clinical effect was analyzed using immunohistochemistry with surgically resected PDAC tissues...
May 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29731878/conversion-of-epithelial-to-mesenchymal-transition-to-mesenchymal-to-epithelial-transition-is-mediated-by-oxygen-concentration-in-pancreatic-cancer-cells
#6
Shuo Chen, Xi Chen, Wei Li, Tao Shan, Wan Run Lin, Jiancang Ma, Xijuan Cui, Wenbin Yang, Gang Cao, Yiming Li, Li Wang, Ya'an Kang
Tumor metastasis is accompanied by a two-stage process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Currently, the exact mechanisms underlying EMT-MET conversion are unclear. In the present study, the mechanisms by which primary sites (hypoxic) and homing sites (normoxic or hyperoxic) participate in EMT-MET conversion were evaluated. Pancreatic cancer cells were grown under different oxygenation conditions. Cell morphology and epithelial (E)-cadherin and vimentin expression were examined...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29719602/leptin-notch-axis-impairs-5-fluorouracil-effects-on-pancreatic-cancer
#7
Adriana Harbuzariu, Ruben Rene Gonzalez-Perez
5-FU chemotherapy is a current strategy to treat pancreatic cancer (PC), but unfortunately chemoresistance is eventually developed in most patients. Obesity is a risk factor for PC that could affect 5-FU effectiveness through the adipokine leptin, which is a known proliferation, survival factor and Notch inducer. We investigated whether leptin signaling affects 5-FU cytotoxicity on PC. To this end, tumorspheres developed from BxPC-3 and MiaPaCa-2 PC cells were treated with 5-FU, leptin, inhibitors for Notch (DAPT) and leptin signaling (IONP-LPrA2) and ATP-binding cassette of proteins (Probenecid)...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719293/pik3r3-promotes-metastasis-of-pancreatic-cancer-via-zeb1-induced-epithelial-mesenchymal-transition
#8
Yun-Peng Peng, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Xin-Chun Liu, Xiao-Le Zhu, Yi Miao
BACKGROUND/AIMS: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. METHODS: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29692736/the-function-and-mechanism-of-long-non-coding-rna-atb-in-cancers
#9
REVIEW
Huizhong Xiao, Fuyou Zhang, Yifan Zou, Jianfa Li, Yuchen Liu, Weiren Huang
Long non-coding RNAs (lncRNAs) are a class of transcriptional RNA molecules with a length of greater than 200 nucleotides that function as regulatory factors in many human diseases. Studies have shown that lncRNAs are involved in multiple cellular processes, including proliferation, apoptosis, migration, and invasion. In this report, a long non-coding RNA-ATB that is overexpressed in various tumor tissues and cell lines was investigated. Recent evidence suggests that ATB is dysfunctional in a variety of cancers, including hepatocellular carcinoma, gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC), prostate cancer, renal cell carcinoma, non-small cell lung cancer (NSCLC), pancreatic cancer, osteosarcoma, and glioma...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29672923/dual-role-of-par-4-in-abrogation-of-emt-and-switching-on-mesenchymal-to-epithelial-transition-met-in-metastatic-pancreatic-cancer-cells
#10
Archana Katoch, Sujit Suklabaidya, Souneek Chakraborty, Debasis Nayak, Reyaz Ur Rasool, Deepak Sharma, Debaraj Mukherjee, Mir Mohd Faheem, Anmol Kumar, Parduman Raj Sharma, Shantibhusan Senapati, Lekha Dinesh Kumar, Anindya Goswami
Epithelial-mesenchymal transition (EMT), a critical event that occurs during invasion and metastatic spread of cancer cells. Here, we conceive a dual mechanism of Par-4-mediated inhibition of EMT and induction of MET in metastatic pancreatic cancer cells. First, we demonstrate that 1,1'-β-D-glucopyranosyl-3,3'-bis(5-bromoindolyl)-octyl methane (NGD16), an N-glycosylated derivative of medicinally important phytochemical 3,3'-diindolylmethane (DIM) abrogates EMT by inducing pro-apoptotic protein Par-4. Induction of Par-4 (by NGD16 or ectopic overexpression) strongly impedes invasion with inhibition of major mesenchymal markers viz...
April 19, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29667486/lncrna-adpgk-as1-promotes-pancreatic-cancer-progression-through-activating-zeb1-mediated-epithelial-mesenchymal-transition
#11
Suzhen Song, Weihua Yu, Sen Lin, Mingbao Zhang, Teng Wang, Shuang Guo, Hongbo Wang
OBJECTIVE: This study was conducted to investigate the effects of ADP dependent glucokinase antisense RNA 1 (ADPGK-AS1)/ miR-205-5p/ zinc finger E-box binding homeobox 1 (ZEB1) on PC cells. METHODS: Differentially expressed lncRNAs and miRNAs in pancreatic cancer (PC) were identified by microarray analysis. In silico ceRNA analysis was conducted to find out the interactions among lncRNAs, miRNAs and mRNAs. Quantitative real-time PCR (qRT-PCR) was utilized to examine the expression of miR-205-5p and lncRNA ADPGK-AS1 in PC and non-cancerous cells...
April 18, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29665670/-the-relationship-between-the-radioresistance-of-pancreatic-cancer-cell-sw1990-and-the-induction-of-the-epithelial-mesenchymal-transition-an-in-vitro-study
#12
Y H Jiang, K Y You, Z F Bi, L T Li, H Q Mo, Y M Liu
Objective: To investigate the relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of the Epithelial-Mesenchymal Transition (EMT). Methods: The radio-resistant pancreatic cancer cell SW1990-R were established by using the method of radiating pancreatic cancer cell SW1990 step by step and repeatedly. Then the changes of the morphology of the cell was observed by inverted phase contrast microscope, the radioresistance of SW1990-R was detected by colony-forming assay, and the apoptosis rate of the two cell lines after radiation were measured by flow cytometry...
March 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#13
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29643475/tumor-derived-exosomal-lnc-sox2ot-promotes-emt-and-stemness-by-acting-as-a-cerna-in-pancreatic-ductal-adenocarcinoma
#14
Zhonghu Li, Peng Jiang, Jie Li, Minjie Peng, Xin Zhao, Xi Zhang, Kai Chen, Yujun Zhang, Hui Liu, Lang Gan, Huaqiang Bi, Ping Zhen, Jin Zhu, Xiaowu Li
Long noncoding RNAs (lncRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal lncRNAs in tumor invasion or metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, we aimed to investigate the detailed roles and mechanisms of tumor-generated exosomes in progression and metastasis of PDAC in vitro and in vivo. We identified a lncRNA-Sox2ot from exosomes of highly invasive PDAC cells, and analyzed the expression of Sox2ot in the plasma samples and found that the plasma exosomal Sox2ot expression was high and correlated with TNM stage and overall survival rate of PDAC patients...
April 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29621546/aberrant-upregulation-of-klk10-promotes-metastasis-via-enhancement-of-emt-and-fak-src-erk-axis-in-pdac
#15
Xiao-Yan Cao, Xiao-Xin Zhang, Min-Wei Yang, Li-Peng Hu, Shu-Heng Jiang, Guang-Ang Tian, Li-Li Zhu, Qing Li, Yong-Wei Sun, Zhi-Gang Zhang
Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC...
April 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29615080/radiotherapy-induced-cell-death-activates-paracrine-hmgb1-tlr2-signaling-and-accelerates-pancreatic-carcinoma-metastasis
#16
Xuelian Chen, Lirong Zhang, Yujie Jiang, Lian Song, Yanfang Liu, Fang Cheng, Xin Fan, Xiongfeng Cao, Aihua Gong, Dongqing Wang, Haitao Zhu
BACKGROUND: Dying cells after irradiation could promote the repopulation of surviving cancer cells leading to tumor recurrence. We aim to define the role of dying cells in promoting pancreatic cancer cells metastasis following radiotherapy. METHODS: Using the transwell system as the in vitro co-culture model, a small number of untreated pancreatic cancer cells were seeded in the upper chamber, while a larger number of lethally treated pancreatic cancer cells were seeded in the lower chamber...
April 3, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29599309/mekk3-sustains-emt-and-stemness-in-pancreatic-cancer-by-regulating-yap-and-taz-transcriptional-activity
#17
Raffaela Santoro, Marco Zanotto, Carmine Carbone, Geny Piro, Giampaolo Tortora, Davide Melisi
BACKGROUND/AIM: Pancreatic cancer is one of the most threatening and poorly understood human malignancies. MEKK3 (MAP3K3) is a serine/threonine kinase activated by different signaling pathways. YAP and TAZ are critical oncogenic effectors in pancreatic cancer. We hypothesized that MEKK3 could sustain pancreatic cancer by inducing YAP/TAZ oncogenic activities. MATERIALS AND METHODS: In Panc1 and AsPC1 pancreatic cancer cell lines MEKK3 was knocked-out (KO) by the CRISPR/Cas9 method...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29587800/inhibiting-yap-expression-suppresses-pancreatic-cancer-progression-by-disrupting-tumor-stromal-interactions
#18
Zhengdong Jiang, Cancan Zhou, Liang Cheng, Bin Yan, Ke Chen, Xin Chen, Liang Zong, Jianjun Lei, Wanxing Duan, Qinhong Xu, Xuqi Li, Zheng Wang, Qingyong Ma, Jiguang Ma
BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression. We and others find that YAP is up-regulated in pancreatic ductal adenocarcinoma (PDAC) and associated with worse prognosis of patients. Activated pancreatic stellate cells (PSCs) forming the components of microenvironment that enhance pancreatic cancer cells (PCs) invasiveness and malignance. However, the role and mechanism of YAP in PDAC tumor-stromal interaction is largely unknown...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29587259/kr%C3%A3-ppel-like-factor-4-inhibits-pancreatic-cancer-epithelial-to-mesenchymal-transition-and-metastasis-by-down-regulating-caveolin-1-expression
#19
Zhonglin Zhu, Zhilong Yu, Jianfeng Wang, Lisheng Zhou, Jing Zhang, Bin Yao, Jin Dou, Zhengjun Qiu, Chen Huang
BACKGROUND/AIMS: Krüppel-like factor 4 (KLF4), a member of the KLF family of zinc finger transcription factors, has been identified as a tumor suppressor gene in a variety of tumors. However, the molecular mechanisms by which KLF4 inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic cancer remain unclear. METHODS: KLF4 expression in pancreatic cancer was analyzed using public datasets (Oncomine and The Cancer Genome Atlas). The expression of KLF4, caveolin-1 (Cav-1), E-cadherin, and vimentin, and their correlations with clinicopathological characteristics were evaluated by immunohistochemistry in pancreatic cancer tissues...
March 21, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29568909/hyperthermia-inhibits-the-motility-of-gemcitabine-resistant-pancreatic-cancer-panc-1-cells-through-the-inhibition-of-epithelial-mesenchymal-transition
#20
Hangbin Jin, Yanyan Zhao, Shirong Zhang, Jianfeng Yang, Xiaofeng Zhang, Shenglin Ma
Pancreatic cancer (PC) is one of the most common types of malignant tumor and the leading cause of cancer‑associated mortality worldwide. The chemotherapeutic drug gemcitabine (GEM) is used as a first‑line chemotherapeutic agent for advanced PC. However, the acquisition of drug resistance is a major limitation of the clinical effect of GEM and commonly leads to increased metastasis. The occurrence of epithelial‑mesenchymal transition (EMT) has been demonstrated to be the underlying mechanism of acquired resistance...
March 16, 2018: Molecular Medicine Reports
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