TRIP6 accelerates the proliferation and invasion of cervical cancer by upregulating oncogenic YAP signaling

Exp Cell Res. 2020 Nov 1;396(1):112248. doi: 10.1016/j.yexcr.2020.112248. Epub 2020 Aug 24.

Abstract

Accumulating evidence has suggested that thyroid hormone receptor interacting protein 6 (TRIP6) is a novel tumor-related regulator that is aberrantly expressed in multiple tumors and contributes to tumor progression and metastasis. Yet, little is known about the role of TRIP6 in cervical cancer. In the current study, we aimed to explore the expression, biological function, and regulatory mechanism of TRIP6 in cervical cancer. Here we showed that TRIP6 expression was markedly upregulated in cervical cancer tissues and cell lines. The knockdown of TRIP6 suppressed the proliferation, colony formation, and invasive potential of cervical cancer cells, whereas TRIP6 overexpression exhibited the opposite effect. Moreover, TRIP6 contributes to the activation of Yes-associated protein (YAP) by downregulating the level of YAP phosphorylation. Notably, TRIP6-mediated tumor promotion effect was partially reversed by YAP inhibition. In addition, TRIP6 knockdown retarded the in vivo tumor growth of cervical cancer of mouse xenograft models associated with downregulation of YAP activation in tumor tissues. Taken together, these results reveal a potential tumor promotion role of TRIP6 that facilitates the proliferation and invasion of cervical cancer through activation of YAP. Our study underlines the importance of the TRIP6/YAP axis in cervical cancer and suggests TRIP6 as a potential anticancer candidate for cervical cancer.

Keywords: Cervical cancer; TRIP6; YAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • LIM Domain Proteins / antagonists & inhibitors
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphorylation
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tumor Burden
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • LIM Domain Proteins
  • RNA, Small Interfering
  • TRIP6 protein, human
  • Transcription Factors
  • YY1AP1 protein, human