TP53INP1 downregulation activates a p73-dependent DUSP10/ERK signaling pathway to promote metastasis of hepatocellular carcinoma

Kai Yu Ng, Lok Hei Chan, Stella Chai, Man Tong, Xin Yuan Guan, Nikki P. Lee, Yunfei Yuan, Dan Xie, Kin Wah Lee, Nelson J. Dusetti, Alice Carrier, Stephanie Ma

Research output: Journal article publicationJournal articleAcademic researchpeer-review

23 Citations (Scopus)

Abstract

Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here, we report that the proapoptotic stress response factor TP53INP1 is often selectively downregulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 downregulation in early-stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings show how TP53INP1 plays a critical role in limiting the progression of early-stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC.
Original languageEnglish
Pages (from-to)4602-4612
Number of pages11
JournalCancer Research
Volume77
Issue number17
DOIs
Publication statusPublished - 1 Sep 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this