EMT as the ultimate survival mechanism of cancer cells

被引:485
作者
Tiwari, Neha [1 ]
Gheldof, Alexander [2 ,3 ]
Tatari, Marianthi [2 ,3 ]
Christofori, Gerhard [1 ]
机构
[1] Univ Basel, Inst Biochem & Genet, Dept Biomed, CH-4058 Basel, Switzerland
[2] Univ Ghent VIB, Dept Mol Biomed Res, B-9052 Ghent, Belgium
[3] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium
关键词
Cancer; EMT; Metastasis; Signaling; Tumorigenesis; EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR RECEPTOR; E-CADHERIN EXPRESSION; REPRESSES E-CADHERIN; NF-KAPPA-B; TRANSCRIPTION FACTOR SNAIL; REGULATES E-CADHERIN; ONCOGENIC K-RAS; TGF-BETA; CONFERS RESISTANCE;
D O I
10.1016/j.semcancer.2012.02.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epithelial cancers make up the vast majority of cancer types and, during the transition from benign adenoma to malignant carcinoma and metastasis, epithelial tumor cells acquire a de-differentiated, migratory and invasive behavior. This process of epithelial-mesenchymal transition (EMT) goes along with dramatic changes in cellular morphology, the loss and remodeling of cell-cell and cell-matrix adhesions, and the gain of migratory and invasive capabilities. EMT itself is a multistage process, involving a high degree of cellular plasticity and a large number of distinct genetic and epigenetic alterations, as fully differentiated epithelial cells convert into poorly differentiated, migratory and invasive mesenchymal cells. In the past years, a plethora of genes have been identified that are critical for EMT and metastasis formation. Notably, the EMT process not only induces increased cancer cell motility and invasiveness but also allows cancer cells to avoid apoptosis, anoikis, oncogene addiction, cellular, senescence and general immune defense. Notably, EMT seems to play a critical role in the generation and maintenance of cancer stem cells, highly consistent with the notion that metastatic cells carry the ability to initiate new tumors. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:194 / 207
页数:14
相关论文
共 230 条
[1]   A Mutant-p53/Smad Complex Opposes p63 to Empower TGFβ-Induced Metastasis [J].
Adorno, Maddalena ;
Cordenonsi, Michelangelo ;
Montagner, Marco ;
Dupont, Sirio ;
Wong, Christine ;
Hann, Byron ;
Solari, Aldo ;
Bobisse, Sara ;
Rondina, Maria Beatrice ;
Guzzardo, Vincenza ;
Parenti, Anna R. ;
Rosato, Antonio ;
Bicciato, Silvio ;
Balmain, Allan ;
Piccolo, Stefano .
CELL, 2009, 137 (01) :87-98
[2]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[3]   Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence [J].
Ansieau, Stephane ;
Bastid, Jeremy ;
Doreau, Agnes ;
Morel, Anne-Pierre ;
Bouchet, Benjamin P. ;
Thomas, Clemence ;
Fauvet, Frederique ;
Puisieux, Isabelle ;
Doglioni, Claudio ;
Piccinin, Sara ;
Maestro, Roberta ;
Voeltzel, Thibault ;
Selmi, Abdelkader ;
Valsesia-Wittmann, Sandrine ;
de Fromentel, Claude Caron ;
Puisieux, Alain .
CANCER CELL, 2008, 14 (01) :79-89
[4]   Epithelial to Mesenchymal Transition Contributes to Drug Resistance in Pancreatic Cancer [J].
Arumugam, Thiruvengadam ;
Ramachandran, Vijaya ;
Fournier, Keith F. ;
Wang, Huamin ;
Marquis, Lauren ;
Abbruzzese, James L. ;
Gallick, Gary E. ;
Logsdon, Craig D. ;
McConkey, David J. ;
Choi, Woonyoung .
CANCER RESEARCH, 2009, 69 (14) :5820-5828
[5]   Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction [J].
Baritaki, S. ;
Chapman, A. ;
Yeung, K. ;
Spandidos, D. A. ;
Palladino, M. ;
Bonavida, B. .
ONCOGENE, 2009, 28 (40) :3573-3585
[6]   The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells [J].
Batlle, E ;
Sancho, E ;
Franci, C ;
Domínguez, D ;
Monfar, M ;
Baulida, J ;
de Herreros, AG .
NATURE CELL BIOLOGY, 2000, 2 (02) :84-89
[7]   The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity [J].
Ben-Saadon, Ronen ;
Zaaroor, Daphna ;
Ziv, Tamar ;
Ciechanover, Aaron .
MOLECULAR CELL, 2006, 24 (05) :701-711
[8]  
Berezovska OP, 2006, CELL CYCLE, V5, P1886
[9]   Activated R-Ras, Rac1, PI 3-kinase and PKC∈ can each restore cell spreading inhibited by isolated integrin β1 cytoplasmic domains [J].
Berrier, AL ;
Mastrangelo, AM ;
Downward, J ;
Ginsberg, M ;
LaFlamme, SE .
JOURNAL OF CELL BIOLOGY, 2000, 151 (07) :1549-1560
[10]   Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize [J].
Bershadsky, Alexander ;
Kozlov, Michael ;
Geiger, Benjamin .
CURRENT OPINION IN CELL BIOLOGY, 2006, 18 (05) :472-481