YY1 cooperates with TFEB to regulate autophagy and lysosomal biogenesis in melanoma

Mol Carcinog. 2019 Nov;58(11):2149-2160. doi: 10.1002/mc.23105. Epub 2019 Aug 26.

Abstract

Autophagy is a self-proteolytic process that degrades intracellular material to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master activator that regulates the transcription of genes involved in autophagy and lysosomal biogenesis. However, the cotranscriptional factors of TFEB are rarely identified. Here, we found that Yin Yang 1 (YY1) regulated autophagy and lysosome biogenesis in melanoma cells. YY1 cooperates with TFEB to regulate autophagy through controlling the transcription of autophagy and lysosome biogenesis related genes. Moreover, suppression of YY1 enhanced the antitumor efficiency of vemurafenib both in vitro and in vivo. Collectively, these studies identify YY1 as a novel cotranscription factor of TFEB in regulating autophagy and lysosomal functions and suggest YY1 could be a therapeutic target in cancer treatment.

Keywords: TFEB; YY1; autophagy; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Heterografts
  • Humans
  • Lysosomes / genetics
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • Plasmids / genetics
  • YY1 Transcription Factor / genetics*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFEB protein, human
  • YY1 Transcription Factor
  • YY1 protein, human