The MiTF/TFE family of transcription factors: Master regulators of organelle signaling, metabolism, and stress adaptation

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Resumen

transcription factors is emerging as global regulators of cancer cell survival and energy metabolism, both through the promotion of lysosomal genes as well as newly characterized targets, such as oxidative metabolism and the oxidative stress response. In addition, MiT/TFE factors can regulate lysosomal signaling, which includes the mTORC1 and Wnt/b-catenin pathways, which are both substantial contributors to oncogenic signaling. This review describes recent discoveries in MiT/TFE research and how they impact multiple cancer subtypes. Furthermore, the literature relating to TFE-fusion proteins in cancers and the potential mechanisms through which these genomic rearrangements promote tumorigenesis is reviewed. Likewise, the emerging function of the Folliculin (FLCN) tumor suppressor in negatively regulating the MiT/TFE family and how loss of this pathway promotes cancer is examined. Recent reports are also presented that relate to the role of MiT/TFE-driven lysosomal biogenesis in sustaining cancer cell metabolism and signaling in nutrient-limiting conditions. Finally, a discussion is provided on the future directions and unanswered questions in the field. In summary, the research surrounding the MiT/TFE family indicates that these transcription factors are promising therapeutic targets and biomarkers for cancers that thrive in stressful niches.

Idioma originalEnglish
Páginas (desde-hasta)1637-1643
Número de páginas7
PublicaciónMolecular Cancer Research
Volumen15
N.º12
DOI
EstadoPublished - dic. 2017

Nota bibliográfica

Funding Information:
This work was funded by grants from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-03687) and Beatrice Hunter Cancer Research Institute seed funding grant (to T. Pulinilkunnil). L. Slade is supported by the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the Canadian Breast Cancer Foundation—Atlantic Region and the New Brunswick Health Research Foundation.

Publisher Copyright:
© 2017 AACR.

ASJC Scopus Subject Areas

  • Molecular Biology
  • Oncology
  • Cancer Research

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, Non-U.S. Gov't

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