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RNF181 modulates Hippo signaling and triple negative breast cancer progression

Rui Zhou1,2, Yinlu Ding3, Min Xue4

  • 1Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Cancer Cell International
|July 14, 2020
PubMed
Abstract

Insights

RNF181 activates Hippo/YAP signaling in triple-negative breast cancer (TNBC), promoting cell growth and metastasis. Inhibiting RNF181 offers a potential therapeutic strategy for TNBC by stabilizing YAP and reducing tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
  • The Hippo/YAP signaling pathway is implicated in TNBC progression.
  • RNF181's role in modulating Hippo/YAP signaling in TNBC requires investigation.

Purpose of the Study:

  • To investigate the role of RNF181 in the modulation of Hippo/YAP signaling in TNBC.
  • To identify RNF181 as a potential therapeutic target for TNBC.

Main Methods:

  • Western blot to measure protein levels (YAP, RNF181).
  • Real-time PCR for Hippo target genes (CTGF, CYR61).
  • Cell proliferation, migration, and invasion assays (WST1, Trans-well, Wound healing).
  • Ubiquitination and protein stability assays to assess YAP regulation.
  • Immunoprecipitation and immunostaining to determine protein interactions and localization.

Main Results:

  • RNF181 positively mediates Hippo/YAP signaling activation in TNBC.
  • RNF181 depletion inhibits TNBC cell proliferation, migration, and invasion.
  • RNF181 interacts with YAP, inhibiting its K48-linked poly-ubiquitination and promoting its stability.
  • Elevated RNF181 expression correlates with poor prognosis in TNBC patients.

Conclusions:

  • RNF181 acts via a non-proteolytic mechanism to modulate Hippo signaling in breast cancer.
  • RNF181 represents a potential prognostic marker and therapeutic target for TNBC.
Keywords:
HippoRNF181TNBCUbiquitinYAP

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