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https://www.readbyqxmd.com/read/28334634/e3-ubiquitin-ligase-cbl-b-prevents-tumor-metastasis-by-maintaining-the-epithelial-phenotype-in-multiple-drug-resistant-gastric-and-breast-cancer-cells
#1
Ling Xu, Ye Zhang, Xiujuan Qu, Xiaofang Che, Tianshu Guo, Ying Cai, Aodi Li, Danni Li, Ce Li, Ti Wen, Yibo Fan, Kezuo Hou, Yanju Ma, Xuejun Hu, Yunpeng Liu
Multiple drug resistance (MDR) and metastasis are two major factors that contribute to the failure of cancer treatment. However, the relationship between MDR and metastasis has not been characterized. Additionally, the role of the E3 ubiquitin ligase Cbl-b in metastasis of MDR gastric and breast cancer is not well known. In the present study, we found that MDR gastric and breast cancer cells possess a typical mesenchymal phenotype and enhanced cell migration capacity. Additionally, Cbl-b is poorly expressed in MDR gastric and breast cancer cells...
March 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28322937/snail-induced-epithelial-to-mesenchymal-transition-enhances-p-gp-mediated-multi-drug-resistance-in-hcc827-cells
#2
Takumi Tomono, Kentaro Yano, Takuo Ogihara
Overexpression and/or activation of P-glycoprotein (P-gp), which mediates efflux transport of various anti-cancer drugs in cancer cells, are associated with multi-drug resistance (MDR). On the other hand, malignant cancer cells frequently undergo epithelial-to-mesenchymal transition (EMT), thereby acquiring high migratory mobility and invasive ability. Snail is a transcriptional factor that represses multiple other factors, and its overexpression is a trigger of EMT. Since both P-gp and Snail are involved in malignant evolution of cancer, in this work, we evaluated whether or not EMT induced by overexpression of Snail influences P-gp expression and/or activity...
March 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#3
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28302417/muc1-c-oncoprotein-integrates-a-program-of-emt-epigenetic-reprogramming-and-immune-evasion-in-human-carcinomas
#4
REVIEW
Hasan Rajabi, Donald Kufe
The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28294486/pd-l1-expression-at-tumor-invasive-front-is-associated-with-emt-and-poor-prognosis-in-esophageal-squamous-cell-carcinoma
#5
Satoshi Tsutsumi, Hiroshi Saeki, Yuichiro Nakashima, Shuhei Ito, Eiji Oki, Masaru Morita, Yoshinao Oda, Shinji Okano, Yoshihiko Maehara
Programmed death-ligand 1 (PD-L1) plays a crucial role in the host immune system in cancer progression. The gene promoter region of PD-L1 also contains a binding site for ZEB1, a transcription factor related to epithelial-mesenchymal transition (EMT). The purpose of this study was to clarify the relationship between PD-L1 and EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). PD-L1 and ZEB1 expression at the tumor invasive front was examined by immunohistochemistry in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy, and their expression and clinicopathological factors were compared...
March 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#6
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28286418/mir-484-suppresses-proliferation-and-epithelial-mesenchymal-transition-by-targeting-zeb1-and-smad2-in-cervical-cancer-cells
#7
Yang Hu, Hong Xie, Yankun Liu, Weiying Liu, Min Liu, Hua Tang
BACKGROUND: MicroRNAs (miRNAs) play important roles in cancer initiation and development. Epithelial-mesenchymal transition (EMT) is a form of cellular plasticity that is critical for embryonic development and metastasis. The purpose of the study was to determine the function and mechanism of miR-484 in initiation and development of cervical cancer (CC). METHODS: We determined the expression levels of miR-484 in cervical cancer tissues and cell lines with RT-qPCR...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#8
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28284480/copy-number-variations-found-in-patients-with-a-corpus-callosum-abnormality-and-intellectual-disability
#9
Solveig Heide, Boris Keren, Thierry Billette de Villemeur, Sandra Chantot-Bastaraud, Christel Depienne, Caroline Nava, Cyril Mignot, Aurélia Jacquette, Eric Fonteneau, Elodie Lejeune, Corinne Mach, Isabelle Marey, Sandra Whalen, Didier Lacombe, Sophie Naudion, Caroline Rooryck, Annick Toutain, Cédric Le Caignec, Damien Haye, Laurence Olivier-Faivre, Alice Masurel-Paulet, Christel Thauvin-Robinet, Fabien Lesne, Anne Faudet, Dorothée Ville, Vincent des Portes, Damien Sanlaville, Jean-Pierre Siffroi, Marie-Laure Moutard, Delphine Héron
OBJECTIVE: To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays. RESULTS: In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype...
March 8, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28282787/long-non-coding-rna-snhg20-predicts-a-poor-prognosis-for-hcc-and-promotes-cell-invasion-by-regulating-the-epithelial-to-mesenchymal-transition
#10
Jinxia Liu, Cuihua Lu, Mingbing Xiao, Feng Jiang, Lishuai Qu, Runzhou Ni
BACKGROUND: Recently, Accumulating evidence indicates that long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human tumor biology and development. However, the expression pattern and biological function of lncRNA small nucleolar RNA host gene 20 (SNHG20) in hepatocellular carcinoma (HCC) remains largely unknown. METHODS: The expression of SNHG20 in 96 paired HCC tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR) analysis...
March 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28281973/abcb5-zeb1-axis-promotes-invasion-and-metastasis-in-breast-cancer-cells
#11
Juntao Yao, Xuan Yao, Tao Tian, Xiao Fu, Wenjuan Wang, Suoni Li, Tingting Shi, Aili Suo, Zhiping Ruan, Hui Guo, Kejun Nan, Xiongwei Huo
ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial-mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes...
March 13, 2017: Oncology Research
https://www.readbyqxmd.com/read/28274892/mir-875-5p-counteracts-epithelial-to-mesenchymal-transition-and-enhances-radiation-response-in-prostate-cancer-through-repression-of-the-egfr-zeb1-axis
#12
Rihan El Bezawy, Denis Cominetti, Nicola Fenderico, Valentina Zuco, Giovanni Luca Beretta, Matteo Dugo, Noemi Arrighetti, Claudio Stucchi, Tiziana Rancati, Riccardo Valdagni, Nadia Zaffaroni, Paolo Gandellini
Radiotherapy is one of the main treatment choices for non-metastatic prostate cancer (PCa), although development of radioresistance limits its effectiveness. Mounting evidence supports the ability of microRNAs to interfere with different radioresistance-associated pathways, suggesting their potential as radiosensitizers. Here, we demonstrate that reconstitution of miR-875-5p, whose expression is down-regulated in PCa clinical samples and directly correlates with that of E-cadherin, was able to enhance radiation response in PCa cell lines and xenografts through EGFR direct targeting...
March 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28270621/integrin-%C3%AE-4-identifies-cancer-stem-cell-enriched-populations-of-partially-mesenchymal-carcinoma-cells
#13
Brian Bierie, Sarah E Pierce, Cornelia Kroeger, Daniel G Stover, Diwakar R Pattabiraman, Prathapan Thiru, Joana Liu Donaher, Ferenc Reinhardt, Christine L Chaffer, Zuzana Keckesova, Robert A Weinberg
Neoplastic cells within individual carcinomas often exhibit considerable phenotypic heterogeneity in their epithelial versus mesenchymal-like cell states. Because carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse, we sought to determine whether such cells could be further stratified into functionally distinct subtypes. Indeed, we find that a basal epithelial marker, integrin-β4 (ITGB4), can be used to enable stratification of mesenchymal-like triple-negative breast cancer (TNBC) cells that differ from one another in their relative tumorigenic abilities...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28266048/the-grhl2-zeb-feedback-loop-a-key-axis-in-the-regulation-of-emt-in-breast-cancer
#14
Steven M Mooney, Vida Talebian, Mohit Kumar Jolly, Dongya Jia, Monica Gromala, Herbert Levine, Brendan J McConkey
More than 90% of cancer-related deaths are caused by metastasis. Epithelial-to-Mesenchymal Transition (EMT) causes tumor cell dissemination while the reverse process, Mesenchymal-to-Epithelial Transition (MET) allows cancer cells to grow and establish a potentially deadly metastatic lesion. Recent evidence indicates that in addition to E and M, cells can adopt a stable hybrid Epithelial/Mesenchymal (E/M) state where they can move collectively leading to clusters of Circulating Tumor Cells - the 'bad actors' of metastasis...
March 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28261684/evaluation-of-zinc-finger-e-box-binding-homeobox-1-and-transforming-growth-factor-beta2-expression-in-bladder-cancer-tissue-in-comparison-with-healthy-adjacent-tissue
#15
Ali Mahdavinezhad, Reza Yadegarazari, Seyed Habibollah Mousavi-Bahar, Jalal Poorolajal, Mohammad Jafari, Mohammad Ali Amirzargar, Hosein Effatpanah, Massoud Saidijam
PURPOSE: The fifth most common cancer is allocated to bladder cancer (BC) worldwide. Understanding the molecular mechanisms of BC invasion and metastasis to identify target therapeutic strategies will improve disease survival. So the aim of this study was to measure expression rate of zinc finger E-box binding homeobox 1 (ZEB1) and transforming growth factor-beta2 (TGF-β2) mRNA in tissue samples of patients with BC and its healthy adjacent tissue samples and their association with muscle invasion, size and grade of the tumor...
March 2017: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/28260066/repression-of-the-expression-of-tet2-by-zeb1-contributes-to-invasion-and-growth-in-glioma-cells
#16
Bo Chen, Yanqing Lei, Hongquan Wang, Yanwei Dang, Peihai Fang, Jun Wang, Jinbo Yang, Lijun Liu
Malignant gliomas are the most common and aggressive type of brain tumor. The suppressive role of ten-eleven translocation 2 (TET2) has been implicated in certain types of cancer, however, its role in gliomas remains to be elucidated. The present study aimed to determine the expression pattern and biological role of TET2 in glioma, using RT-qPCR and immunohistochemistry, and its results indicated that the expression of TET2 was frequently decreased in gliomas and that repression of the expression of TET2 correlated with the progression of glioma...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28247944/ets1-and-ese1-reciprocally-regulate-expression-of-zeb1-zeb2-dependently-on-erk1-2-activity-in-breast-cancer-cells
#17
Nguyen Duy Sinh, Kaori Endo, Keiji Miyazawa, Masao Saitoh
The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during progression of epithelial tumors. We reported previously that levels of the δEF1 family proteins (ZEB1/δEF1 and ZEB2/SIP1), key regulators of the EMT, are positively correlated with EMT phenotypes and aggressiveness of breast cancer. Here, we show that Ets1 induces ZEB expression and activates the ZEB1 promoter, independently of its threonine 38 phosphorylation status. In the basal-like subtype of breast cancer cells, siRNAs targeting Ets1 repressed expression of ZEBs and partially restored their epithelial phenotypes and sensitivity to anti-tumor drugs...
March 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28246407/zeb1-regulates-glioma-stemness-through-lif-repression
#18
Lincoln A Edwards, Aiguo Li, Dror Berel, Mecca Madany, Nam-Ho Kim, Minzhi Liu, Mitch Hymowitz, Benjamin Uy, Rachel Jung, Minlin Xu, Keith L Black, Altan Rentsendorj, Xuemo Fan, Wei Zhang, John S Yu
The identification of a stem cell regulatory gene which is aberrantly expressed in glioma and associated with patient survival would increase the understanding of the role of glioma cancer stem cells (GCSCs) in the virulence of gliomas. Interrogating the genomes of over 4000 brain cancers we identified ZEB1 deletion in ~15% (grade II and III) and 50% of glioblastomas. Meta-analysis of ZEB1 copy number status in 2,988 cases of glioma revealed disruptive ZEB1 deletions associated with decreased survival. We identified ZEB1 binding sites within the LIF (stemness factor) promoter region, and demonstrate LIF repression by ZEB1...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246385/zeb1-regulates-multiple-oncogenic-components-involved-in-uveal-melanoma-progression
#19
Yao Chen, Xiaoqin Lu, Diego E Montoya-Durango, Yu-Hua Liu, Kevin C Dean, Douglas S Darling, Henry J Kaplan, Douglas C Dean, Ling Gao, Yongqing Liu
Human uveal melanoma (UM) is a major ocular malignant tumor with high risk of metastasis and requires multiple oncogenic factors for progression. ZEB1 is a zinc finger E-box binding transcription factor known for participating epithelial-mesenchymal transition (EMT), a critical cellular event for metastasis of malignant tumors of epithelium origin. ZEB1 is also expressed in UM and high expression of ZEB1 correlates with UM advancement, but has little effect on cell morphology. We show that spindle UM cells can become epithelioid but not vice versa; and ZEB1 exerts its tumorigenic effects by promoting cell dedifferentiation, proliferation, invasiveness, and dissemination...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225782/chronic-treatment-of-non-small-cell-lung-cancer-cells-with-gefitinib-leads-to-an-epigenetic-loss-of-epithelial-properties-associated-with-reductions-in-microrna-155-and-200c
#20
Michiko Narita, Eri Shimura, Atsumi Nagasawa, Toshiki Aiuchi, Yukari Suda, Yusuke Hamada, Daigo Ikegami, Chizuru Iwasawa, Kazuhiko Arakawa, Katsuhide Igarashi, Naoko Kuzumaki, Yusuke Yoshioka, Takahiro Ochiya, Hideyuki Takeshima, Toshikazu Ushijima, Minoru Narita
BACKGROUND: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells. METHODS AND RESULTS: To establish gefitinib-resistant NSCLC cells, gefitinib-sensitive HCC827 cells, which exhibit an in-frame deletion [E746-A750] in EGFR exon 19, were exposed to gefitinib for at least 1...
2017: PloS One
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