Emerging roles of the MiT/TFE factors in cancer

Trends Cancer. 2023 Oct;9(10):817-827. doi: 10.1016/j.trecan.2023.06.005. Epub 2023 Jul 1.


The microphthalmia/transcription factor E (MiT/TFE) transcription factors (TFs; TFEB, TFE3, MITF, and TFEC) play a central role in cellular catabolism and quality control and are subject to extensive layers of regulation that influence their localization, stability, and activity. Recent studies have highlighted a broader role for these TFs in driving diverse stress-adaptation pathways, which manifest in a context- and tissue-dependent manner. Several human cancers upregulate the MiT/TFE factors to survive extreme fluctuations in nutrients, energy, and pharmacological challenges. Emerging data suggest that reduced activity of the MiT/TFE factors can also promote tumorigenesis. Here, we outline recent findings relating to novel mechanisms of regulation and activity of MiT/TFE proteins across some of the most aggressive human cancers.

Keywords: TFE3; TFEB; autophagy; cancer; lysosome; mTORC1; metabolism.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Humans
  • Lysosomes / metabolism
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Microphthalmos* / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / metabolism


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Microphthalmia-Associated Transcription Factor