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PSMD14 promotes breast cancer progression by reducing K63-linked ubiquitination on FOXM1 and activating the

Yuhan Liu1, Shichao Wen1, Wenmeng Wang2

  • 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.

International Journal of Biological Macromolecules
|September 3, 2025
PubMed

Insights

The 26S proteasome subunit PSMD14 drives breast cancer progression by deubiquitinating FOXM1 and activating the PI3K/AKT/mTOR pathway. This highlights PSMD14 as a potential therapeutic target for breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinating enzyme (DUB), is implicated in various cancers.
  • The specific role and molecular mechanisms of PSMD14 in breast cancer are not fully understood.

Purpose of the Study:

  • To investigate the oncogenic role of PSMD14 in breast cancer.
  • To elucidate the molecular mechanisms underlying PSMD14's function in breast cancer progression.

Main Methods:

  • Analysis of public databases for PSMD14 expression and prognostic value.
  • In vitro and in vivo functional assays (proliferation, migration, invasion).
  • Co-immunoprecipitation, immunofluorescence, and deubiquitination assays to determine molecular mechanisms, including interaction with FOXM1 and pathway activation (PI3K/AKT/mTOR).

Main Results:

  • Elevated PSMD14 expression correlates with poor prognosis in breast cancer patients.
  • PSMD14 significantly promotes breast cancer cell proliferation, migration, and invasion.
  • PSMD14 directly deubiquitinates FOXM1 (K63-linked) and activates the PI3K/AKT/mTOR pathway.
  • PSMD14 enhances sensitivity to Cisplatin treatment.

Conclusions:

  • PSMD14 promotes breast cancer progression via deubiquitination of FOXM1 and activation of the PI3K/AKT/mTOR pathway.
  • PSMD14 is a potential therapeutic target for breast cancer intervention.
Keywords:
Breast cancerCisplatin chemosensitivityDeubiquitinationFOXM1PI3K/AKT/mTOR pathwayPSMD14

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