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

Kaiqiang LI; Yimin YANG; Yaling WANG; Jing JIN; Qianni WANG; Lina PENG; Aibo XU; Xuling LUO; Wei YANG; Peng XU; Bingyu CHEN; Ke HAO; Zhen WANG

doi:10.1631/jzus.B2400167

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Research Article | Updated：2026-01-27

PICK1 modulates the proliferation and migration of gastric cancer cells by regulating TLR4
PICK1 modulates the proliferation and migration of gastric cancer cells by regulating TLR4
PICK1通过调控TLR4影响胃癌细胞的增殖和迁移
Journal of Zhejiang University-SCIENCE B Vol. 27, Issue 1, Pages: 58-72(2026)
Affiliations：

1.Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, China
2.Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou 310063, China
3.College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China
4.Department of Biophysics and Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
5.The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China
Funds：
DOI：10.1631/jzus.B2400167
CLC：
CSTR：
Received：25 March 2024，

Revised：2024-09-23，

Published Online：29 November 2025，

Published：27 January 2026
Accepted：

李凯强,杨益敏,王娅玲等.,PICK1通过调控,TLR4影响胃癌细胞的增殖和迁移[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(01):58-72.

Kaiqiang LI, Yimin YANG, Yaling WANG, et al. PICK1 modulates the proliferation and migration of gastric cancer cells by regulating TLR4[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(1): 58-72.
李凯强,杨益敏,王娅玲等.,PICK1通过调控,TLR4影响胃癌细胞的增殖和迁移[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(01):58-72. DOI： 10.1631/jzus.B2400167.

Kaiqiang LI, Yimin YANG, Yaling WANG, et al. PICK1 modulates the proliferation and migration of gastric cancer cells by regulating TLR4[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(1): 58-72. DOI： 10.1631/jzus.B2400167.

摘要

蛋白激酶C相互作用蛋白1（PICK1）与多种参与神经系统疾病和多种癌症的膜蛋白和受体存在相互作用。然而，PICK1在胃癌中的作用仍不清楚。本研究旨在探讨PICK1在胃癌中的表达以及与Toll样受体4（TLR4）的相互作用。临床数据分析显示，肿瘤部位PICK1表达水平下降，可预测胃癌患者不良预后。高表达PICK1可抑制胃癌细胞的增殖和迁移，该作用依赖于TLR4/MyD88信号通路。此外，体外实验表明，PICK1影响TLR4的转运和降解，并通过自噬促进胃癌细胞中TLR4的降解。分子动力学模拟强调了TLR4-PICK1复合物的结合强度和稳定性。本研究为阐明PICK1在胃癌中的细胞和病理功能提供了新的见解。

Abstract

Protein interacting with C kinase 1 (PICK1) interacts with a variety of membrane proteins and receptors involved in nervous system diseases and multiple cancers. However

the role of PICK1 in gastric cancer remains unclear. In the present work

we explored the expression and interactions of PICK1 with Toll-like receptor 4 (TLR4) in gastric cancer. Clinical data analysis showed that PICK1 expression decreases and is predictive of worse outcomes in patients with gastric cancer. High PICK1 levels attenuate the proliferation and migration of gastric cancer cells

which is dependent on the TLR4/myeloid differentiation primary response 88 (MyD88) signaling pathway. Furthermore

in vitro experiments demonstrated that PICK1 affects the trafficking and degradation of TLR4 and promotes TLR4 degradation via autophagy in gastric cancer cells. Molecular dynamics simulations highlighted the binding strength and stability of the TLR4-PICK1 complex. Our study provides new insights into the cellular and pathological functions of PICK1 in gastric cancer.

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references

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