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PICK1 modulates the proliferation and migration of gastric cancer cells by regulating TLR4

Kaiqiang Li1,2, Yimin Yang3, Yaling Wang1

  • 1Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China.

Journal of Zhejiang University. Science. B
|January 28, 2026
PubMed

Insights

Protein Interacting with C Kinase 1 (PICK1) is downregulated in gastric cancer, hindering cell proliferation and migration. PICK1 influences Toll-like Receptor 4 (TLR4) degradation, offering new therapeutic insights.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Protein Interacting with C Kinase 1 (PICK1) is implicated in various diseases, but its role in gastric cancer is not well understood.
  • PICK1 interacts with numerous membrane proteins and receptors relevant to cancer and neurological disorders.

Purpose of the Study:

  • To investigate the expression and functional role of PICK1 in gastric cancer.
  • To explore the interaction between PICK1 and Toll-like Receptor 4 (TLR4) in gastric cancer progression.

Main Methods:

  • Clinical data analysis of PICK1 expression and patient outcomes.
  • In vitro experiments assessing the impact of PICK1 on gastric cancer cell proliferation and migration.
  • Investigation of the TLR4/MyD88 signaling pathway.
  • In vitro experiments on TLR4 trafficking and degradation.
  • Molecular dynamics simulations of the TLR4-PICK1 complex.

Main Results:

  • Decreased PICK1 expression correlates with poorer outcomes in gastric cancer patients.
  • High PICK1 levels inhibit gastric cancer cell proliferation and migration via the TLR4/MyD88 pathway.
  • PICK1 influences TLR4 trafficking and promotes its degradation through autophagy in gastric cancer cells.
  • Molecular dynamics simulations confirm the binding stability of the TLR4-PICK1 complex.

Conclusions:

  • PICK1 plays a protective role in gastric cancer by attenuating cancer cell proliferation and migration.
  • PICK1-mediated regulation of TLR4 degradation is a key mechanism in its anti-cancer effects.
  • This study elucidates novel functions of PICK1 in gastric cancer, highlighting its potential as a therapeutic target.
Keywords:
AutophagyGastric cancerMyeloid differentiation primary response 88 (MyD88) signaling pathwayProtein interacting with C kinase 1 (PICK1)Toll-like receptor 4 (TLR4)

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