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Updated: May 4, 2026

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
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Targeting the ZDHHC9-mediated STAT1 palmitoylation-phosphorylation conversion inhibits gastric cancer progression

Xiao Bai1, Yun-Ran Guo2, Wan-Chuan Zhang3

  • 1Department of Surgical Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.

Journal of Gastroenterology
|February 19, 2026
PubMed
Abstract

Insights

ZDHHC9 promotes gastric cancer (GC) by palmitoylating STAT1, affecting its phosphorylation and driving tumor growth. Inhibiting this process offers a potential therapeutic strategy for GC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Palmitoyl transferases (ZDHHCs) and protein palmitoylation are implicated in various cancers.
  • The specific role of ZDHHCs and palmitoylation in gastric cancer (GC) remains largely unknown.

Purpose of the Study:

  • To investigate the role of ZDHHCs and protein palmitoylation in gastric cancer.
  • To elucidate the underlying molecular mechanisms involving ZDHHC9 and STAT1 in GC progression.

Main Methods:

  • Utilized acyl-biotinyl exchange assay, co-immunoprecipitation, immunohistochemistry, western blot, immunofluorescence, and confocal imaging.
  • Employed ZDHHC9 gene silencing and a palmitoylation inhibitor (2-bromopalmitate).

Main Results:

  • Identified widespread protein palmitoylation in GC; 2-bromopalmitate inhibited GC progression.
  • Found abnormal ZDHHC9 overexpression associated with poor GC prognosis; ZDHHC9 silencing inhibited GC growth and induced apoptosis.
  • Demonstrated ZDHHC9 mediates STAT1 S-palmitoylation at Cys577 and Tyr701 phosphorylation via the JAK1-STAT1 pathway, driving GC progression.

Conclusions:

  • ZDHHC9 promotes GC progression by regulating STAT1 S-palmitoylation and phosphorylation.
  • The ZDHHC9-STAT1 axis represents a potential therapeutic target for gastric cancer treatment.
Keywords:
Gastric cancerSTAT1 palmitoylationZDHHC9

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