A feed forward loop enforces YAP/TAZ signaling during tumorigenesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

6 Scopus Citations
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Author(s)

  • Mandeep K. Gill
  • Tania Christova
  • Ying Y. Zhang
  • Alex Gregorieff
  • Masahiro Narimatsu
  • Siyuan Song
  • Shawn Xiong
  • Amber L. Couzens
  • Jiefei Tong
  • Jonathan R. Krieger
  • Michael F. Moran
  • Alexandre R. Zlotta
  • Theodorus H. van der Kwast
  • Anne-Claude Gingras
  • Frank Sicheri
  • Jeffrey L. Wrana
  • Liliana Attisano

Detail(s)

Original languageEnglish
Article number3510
Journal / PublicationNature Communications
Volume9
Online published29 Aug 2018
Publication statusPublished - Aug 2018

Link(s)

Abstract

In most solid tumors, the Hippo pathway is inactivated through poorly understood mechanisms that result in the activation of the transcriptional regulators, YAP and TAZ. Here, we identify NUAK2 as a YAP/TAZ activator that directly inhibits LATS-mediated phosphorylation of YAP/TAZ and show that NUAK2 induction by YAP/TAZ and AP-1 is required for robust YAP/TAZ signaling. Pharmacological inhibition or loss of NUAK2 reduces the growth of cultured cancer cells and mammary tumors in mice. Moreover, in human patient samples, we show that NUAK2 expression is elevated in aggressive, high-grade bladder cancer and strongly correlates with a YAP/TAZ gene signature. These findings identify a positive feed forward loop in the Hippo pathway that establishes a key role for NUAK2 in enforcing the tumor-promoting activities of YAP/TAZ. Our results thus introduce a new opportunity for cancer therapeutics by delineating NUAK2 as a potential target for re-engaging the Hippo pathway.

Research Area(s)

Citation Format(s)

A feed forward loop enforces YAP/TAZ signaling during tumorigenesis. / Gill, Mandeep K.; Christova, Tania; Zhang, Ying Y.; Gregorieff, Alex; Zhang, Liang; Narimatsu, Masahiro; Song, Siyuan; Xiong, Shawn; Couzens, Amber L.; Tong, Jiefei; Krieger, Jonathan R.; Moran, Michael F.; Zlotta, Alexandre R.; van der Kwast, Theodorus H.; Gingras, Anne-Claude; Sicheri, Frank; Wrana, Jeffrey L.; Attisano, Liliana.

In: Nature Communications, Vol. 9, 3510, 08.2018.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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