ZEB/miR‐200 feedback loop: At the crossroads of signal transduction in cancer

• Published in: International journal of cancer Vol. 132; no. 4; pp. 745 - 754
• Main Authors: Hill, Louise, Browne, Gareth, Tulchinsky, Eugene
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-02-2013; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Animals; Biological and medical sciences; Cancer; Carcinogenesis, carcinogens and anticarcinogens; Cell Differentiation; Cell Transformation, Neoplastic - metabolism; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition; Feedback, Physiological; Gene Expression Regulation, Neoplastic; General aspects; Homeodomain Proteins - metabolism; Humans; Medical sciences; MicroRNAs - metabolism; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - metabolism; Proteins; Repressor Proteins - metabolism; Signal Transduction; Transcription Factors - metabolism; Tumors; ZEB proteins; Zinc Finger E-box Binding Homeobox 2; Zinc Finger E-box-Binding Homeobox 1; Human; ZEB proteins; RNA interference; Micro RNA; Malignant tumor; Cell transformation; Carcinogenesis; Gene silencing; Signal transduction; Cancerology; Feedback; Epithelial mesenchymal transition; Transcription factor; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.27708

Embryonic differentiation programs of epithelial–mesenchymal and mesenchymal–epithelial transition (EMT and MET) represent a mechanistic basis for epithelial cell plasticity implicated in cancer. Transcription factors of the ZEB protein family (ZEB1 and ZEB2) and several microRNA species (predominantly miR‐200 family members) form a double negative feedback loop, which controls EMT and MET programs in both development and tumorigenesis. In this article, we review crosstalk between the ZEB/miR‐200 axis and several signal transduction pathways activated at different stages of tumor development. The close association of ZEB proteins with these pathways is indirect evidence for the involvement of a ZEB/miR‐200 loop in tumor initiation, progression and spread. Additionally, the configuration of signaling pathways involving ZEB/miR‐200 loop suggests that ZEB1 and ZEB2 may have different, possibly even opposing, roles in some forms of human cancer.