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Updated: Sep 11, 2025

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
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USP44 Regulates Chemoresistance Induced by ROS and the MAPK/NF-κB Pathway Through the Stabilization of ITGB4 in

Wanting Xiao1, Yuming Lou1, Pu Wu2

  • 1Department of Breast and Thyroid Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 18, 2025
PubMed

Insights

Ubiquitin-specific peptidase 44 (USP44) stabilizes ITGB4, reducing cisplatin resistance in gastric cancer. This finding reveals USP44 as a potential therapeutic target for improving chemotherapy effectiveness in gastric cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cisplatin resistance significantly hinders gastric cancer (GC) treatment success.
  • Deubiquitinase enzymes play a key role in cancer drug resistance.
  • The specific role of USP44 in GC and cisplatin resistance was unclear.

Purpose of the Study:

  • To investigate the role of USP44 in gastric cancer cisplatin resistance.
  • To identify USP44 targets and elucidate the underlying mechanisms.
  • To evaluate USP44 as a potential therapeutic target for GC.

Main Methods:

  • Proteomic analysis to identify USP44 substrates.
  • Assessing USP44 expression in GC tissues.
  • Investigating the effects of USP44/ITGB4 on cellular pathways (ROS, MAPK/NF-κB) and chemoresistance markers (P-gp).

Main Results:

  • USP44 was significantly upregulated in GC tissues and correlated with patient survival.
  • ITGB4 was identified as a novel substrate of USP44.
  • USP44 deubiquitination stabilized ITGB4, reducing cisplatin resistance by modulating ROS and MAPK/NF-κB signaling.
  • ITGB4 influenced P-gp expression and antioxidant enzyme activity, promoting cisplatin efflux and chemoresistance.

Conclusions:

  • USP44 stabilizes ITGB4, conferring cisplatin resistance in gastric cancer.
  • USP44 and ITGB4 represent a novel mechanism driving chemoresistance in GC.
  • USP44 is a promising therapeutic target for overcoming cisplatin resistance in gastric cancer.
Keywords:
ITGB4MAPK/NF‐κB signaling pathwayUSP44chemoresistancegastric cancerubiquitylation

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