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Updated: Aug 24, 2025

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RBCK1 is an endogenous inhibitor for triple negative breast cancer via hippo/YAP axis

Zhongbo Li1, Peng Su2, Yinlu Ding3

  • 1Xinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan Province, People's Republic of China.

Cell Communication and Signaling : CCS
|October 25, 2022
PubMed
Abstract

Insights

RBCK1 inhibits triple-negative breast cancer (TNBC) progression by stabilizing YAP protein. This discovery offers a new therapeutic target for TNBC, a lethal cancer subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies, necessitating novel treatment strategies.
  • The Hippo/YAP signaling pathway is implicated in TNBC development and progression.
  • RBCK1, previously linked to other cancers and immune responses, has an unclear role in TNBC.

Discussion:

  • This study investigates the role of RBCK1 in TNBC, contrasting its known functions in other breast cancer subtypes.
  • The research explores the molecular mechanisms by which RBCK1 influences TNBC cell behavior and the Hippo/YAP pathway.
  • Experimental data are presented to elucidate the interaction between RBCK1 and YAP.

Key Insights:

  • RBCK1 overexpression suppresses TNBC cell proliferation in vitro and in vivo, while RBCK1 depletion enhances invasion.
  • RBCK1 depletion activates the Hippo/YAP axis, increasing YAP protein levels and downstream target gene expression.
  • RBCK1 stabilizes YAP protein through K48-linked poly-ubiquitination at specific lysine residues, thereby inhibiting TNBC progression.

Outlook:

  • RBCK1 demonstrates a dual role in breast cancer, acting as a suppressor in TNBC but a promoter in luminal subtypes.
  • These findings identify RBCK1 as a potential therapeutic target for TNBC.
  • Further research may explore therapeutic interventions targeting the RBCK1-YAP interaction in TNBC.
Keywords:
Breast cancerRBCK1UbiquitinYAP

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