PICALM exerts a role in promoting CRC progression through ERK/MAPK signaling pathway

Xitao Zhang; Tianlai Liu; Jinlin Huang; Jianping He

doi:10.1186/s12935-022-02577-z

PICALM exerts a role in promoting CRC progression through ERK/MAPK signaling pathway

Cancer Cell Int. 2022 May 2;22(1):178. doi: 10.1186/s12935-022-02577-z.

Authors

Xitao Zhang¹, Tianlai Liu¹, Jinlin Huang², Jianping He³

Affiliations

¹ Department of Coloproctology, Zhujiang Hospital, Southern Medical University, 253 Gongye Middle Avenue, Haizhu, Guangzhou, 510280, Guangdong, China.
² Department of General Surgery, Shun De Hospital of Guang Zhou University of Chinese Medicine, 898 Jinsha Avenue, Shun De, Foshan, 510006, Guangdong, China.
³ Department of Coloproctology, Zhujiang Hospital, Southern Medical University, 253 Gongye Middle Avenue, Haizhu, Guangzhou, 510280, Guangdong, China. hejp@smu.edu.cn.

Abstract

Background: Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract with high incidence and mortality. In this study, the functions and potential mechanism of phosphatidylinositol-binding clathrin assembly protein (PICALM) in CRC were preliminarily explored.

Methods: Based on the Cancer Genome Atlas database and immunohistochemistry staining, revealing that the expression level of PICALM in CRC tissues was higher than that in adjacent normal tissues.

Results: Moreover, loss-of-function and gain-of-function assays in HCT 116 and RKO cells found that PICALM promotes proliferation and migration of CRC cells and inhibits apoptosis. Consistently, knockdown of PICALM inhibited tumorigenicity of CRC cells in vivo. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that knockdown of PICALM resulted in the enrichment of MAPK signaling pathway. Treatment of CRC cells with MAPK inhibitor reversed the effects of PICALM overexpression on proliferation and apoptosis. In addition, overexpression of PICALM upregulated the protein levels of ERK1/2 (p-ERK1/2), MEK1/2 (p-MEK1/2), p38 (p-p38) and JNK (p-JNK), and these effects were partially alleviated by the treatment of MAPK inhibitor.

Conclusions: In summary, the study presented the new discovery that PICALM promoted CRC progression through ERK/MAPK signaling pathway, which drew further interest regarding its clinical application as a promising therapeutic target.

Keywords: Apoptosis; CRC; MAPK; Migration; PICALM; Proliferation.