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On-line Access: 2024-11-05

Received: 2024-03-25

Revision Accepted: 2024-09-23

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Citations:  Bibtex RefMan EndNote GB/T7714

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Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)


PICK1 modulates proliferation and migration of gastric cancer cells via regulating TLR4


Author(s):  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

Affiliation(s):  Laboratory Medicine Center, Allergy center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, China; more

Corresponding email(s):  wangzhen@hmc.edu.cn, haoke@hmc.edu.cn, chenbingyu@hmc.edu.cn

Key Words:  Protein interacting with C kinase 1; Gastric cancer; Toll-like receptor 4; MYD88 signalling pathway; Autophagy


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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 attenuated the proliferation and migration of gastric cancer cells, which is dependent on the TLR4/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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