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

Publication ,  Journal Article
Yang, W-H; Ding, C-KC; Sun, T; Rupprecht, G; Lin, C-C; Hsu, D; Chi, J-T
Published in: Cell Rep
September 3, 2019

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 3, 2019

Volume

28

Issue

10

Start / End Page

2501 / 2508.e4

Location

United States

Related Subject Headings

  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Trans-Activators
  • Signal Transduction
  • Receptors, Cell Surface
  • Protein Serine-Threonine Kinases
  • Piperazines
  • Neoplasm Proteins
  • NADPH Oxidase 4
  • Mice
  • Kidney Neoplasms
 

Citation

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Yang, W.-H., Ding, C.-K., Sun, T., Rupprecht, G., Lin, C.-C., Hsu, D., & Chi, J.-T. (2019). The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma. Cell Rep, 28(10), 2501-2508.e4. https://doi.org/10.1016/j.celrep.2019.07.107
Yang, Wen-Hsuan, Chien-Kuang Cornelia Ding, Tianai Sun, Gabrielle Rupprecht, Chao-Chieh Lin, David Hsu, and Jen-Tsan Chi. “The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma.Cell Rep 28, no. 10 (September 3, 2019): 2501-2508.e4. https://doi.org/10.1016/j.celrep.2019.07.107.
Yang W-H, Ding C-KC, Sun T, Rupprecht G, Lin C-C, Hsu D, et al. The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma. Cell Rep. 2019 Sep 3;28(10):2501-2508.e4.
Yang, Wen-Hsuan, et al. “The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma.Cell Rep, vol. 28, no. 10, Sept. 2019, pp. 2501-2508.e4. Pubmed, doi:10.1016/j.celrep.2019.07.107.
Yang W-H, Ding C-KC, Sun T, Rupprecht G, Lin C-C, Hsu D, Chi J-T. The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma. Cell Rep. 2019 Sep 3;28(10):2501-2508.e4.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 3, 2019

Volume

28

Issue

10

Start / End Page

2501 / 2508.e4

Location

United States

Related Subject Headings

  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Trans-Activators
  • Signal Transduction
  • Receptors, Cell Surface
  • Protein Serine-Threonine Kinases
  • Piperazines
  • Neoplasm Proteins
  • NADPH Oxidase 4
  • Mice
  • Kidney Neoplasms