RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer

Huijie Yang1, Min Xue2, Peng Su3

  • 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.

Abstract

Insights

RING finger protein 31 (RNF31) suppresses tumors in triple-negative breast cancer (TNBC) by inhibiting the Hippo/YAP pathway. Activating RNF31 may offer a new therapeutic strategy for TNBC, potentially improving immunotherapy response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Hippo signaling pathway abnormalities are common in triple-negative breast cancer (TNBC) and drive cancer progression.
  • RING finger protein 31 (RNF31), an E3 ubiquitin ligase, is known to be elevated in ER-positive breast cancer.
  • Previous research indicated RNF31's role in activating estrogen signaling and suppressing the P53 pathway in ER-positive breast cancer.

Purpose of the Study:

  • To investigate the function of RNF31 in the progression of triple-negative breast cancer (TNBC).
  • To explore the potential of RNF31 as a therapeutic target for TNBC.

Main Methods:

  • Utilized TNBC cell lines and xenograft models for in vitro and in vivo studies.
  • Performed immuno-blots, QPCR, and global genomic expression profiling.
  • Conducted molecular biology assays to examine protein interactions and ubiquitination.

Main Results:

  • RNF31 exhibits a tumor-suppressive function in TNBC, with RNF31 depletion increasing cell proliferation and migration.
  • RNF31 depletion upregulates YAP protein and Hippo signaling target genes, indicating Hippo signaling as a target.
  • RNF31 expression correlates with longer relapse-free survival in TNBC patients and represses PDL1 expression, sensitizing TNBC to immunotherapy via the Hippo/YAP/PDL1 axis.

Conclusions:

  • RNF31 plays a multifaceted role in different breast cancer subtypes.
  • Activation of RNF31 presents a potential therapeutic strategy for TNBC.
  • Targeting the Hippo/YAP/PDL1 axis through RNF31 modulation could enhance TNBC immunotherapy outcomes.

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