Biology and Clinical Relevance of the Micropthalmia Family of Transcription Factors in Human Cancer

• Published in: Journal of clinical oncology Vol. 29; no. 25; pp. 3474 - 3482
• Main Authors: HAQ, Rizwan, FISHER, David E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.09.2011
• Subjects: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Biological and medical sciences; Carcinogenesis; Humans; Medical sciences; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; Neoplasms - diagnosis; Neoplasms - metabolism; Neoplasms - therapy; Tumors; Human; Signal transduction; Cancerology; Clinical biology; Malignant tumor; Transcription factor; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.32.6223

Members of the micropthalmia (MiT) family of transcription factors (MITF, TFE3, TFEB, and TFEC) are physiologic regulators of cell growth, differentiation, and survival in several tissue types. Because their dysregulation can lead to melanoma, renal cell carcinoma, and some sarcomas, understanding why these genes are co-opted in carcinogenesis may be of general utility. Here we describe the structure of the MiT family of proteins, the ways in which they are aberrantly activated, and the molecular mechanisms by which they promote oncogenesis. We discuss how meaningful understanding of these mechanisms can be used to elucidate the oncogenic process. Because the expression of these proteins is essential for initiating and maintaining the oncogenic state in some cancer types, we propose ways that they can be exploited to prevent, diagnose, and rationally treat these malignancies.