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.

Key words: Protein interacting with C kinase 1 (PICK1); Gastric cancer; Toll-like receptor 4 (TLR4); Myeloid differentiation primary response 88 (MyD88) signaling pathway; Autophagy

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