The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma.

Published

Journal Article

Despite recent advances, the poor outcomes in renal cell carcinoma (RCC) suggest novel therapeutics are needed. Ferroptosis is a form of regulated cell death, which may have therapeutic potential toward RCC; however, much remains unknown about the determinants of ferroptosis susceptibility. We found that ferroptosis susceptibility is highly influenced by cell density and confluency. Because cell density regulates the Hippo-YAP/TAZ pathway, we investigated the roles of the Hippo pathway effectors in ferroptosis. TAZ is abundantly expressed in RCC and undergoes density-dependent nuclear or cytosolic translocation. TAZ removal confers ferroptosis resistance, whereas overexpression of TAZS89A sensitizes cells to ferroptosis. Furthermore, TAZ regulates the expression of Epithelial Membrane Protein 1 (EMP1), which, in turn, induces the expression of nicotinamide adenine dinucleotide phosphate (NADPH) Oxidase 4 (NOX4), a renal-enriched reactive oxygen species (ROS)-generating enzyme essential for ferroptosis. These findings reveal that cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for RCC and other TAZ-activated tumors.

Full Text

Duke Authors

Cited Authors

  • Yang, W-H; Ding, C-KC; Sun, T; Rupprecht, G; Lin, C-C; Hsu, D; Chi, J-T

Published Date

  • September 3, 2019

Published In

Volume / Issue

  • 28 / 10

Start / End Page

  • 2501 - 2508.e4

PubMed ID

  • 31484063

Pubmed Central ID

  • 31484063

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.07.107

Language

  • eng

Conference Location

  • United States