Zhang Xitao, Liu Tianlai, Huang Jinlin, He Jianping
Department of Coloproctology, Zhujiang Hospital, Southern Medical University, 253 Gongye Middle Avenue, Haizhu, Guangzhou, 510280, Guangdong, China.
Department of General Surgery, Shun De Hospital of Guang Zhou University of Chinese Medicine, 898 Jinsha Avenue, Shun De, Foshan, 510006, Guangdong, China.
Cancer Cell Int. 2022 May 2;22(1):178. doi: 10.1186/s12935-022-02577-z.
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.
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.
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.
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.
结直肠癌（CRC）是胃肠道常见的恶性肿瘤，发病率和死亡率都很高。本研究初步探讨了磷脂酰肌醇结合网格蛋白组装蛋白（PICALM）在结直肠癌中的功能及潜在机制。
基于癌症基因组图谱数据库和免疫组化染色，发现PICALM在结直肠癌组织中的表达水平高于相邻正常组织。
此外，在HCT 116和RKO细胞中进行的功能缺失和功能获得实验发现，PICALM促进结直肠癌细胞的增殖和迁移并抑制其凋亡。同样，敲低PICALM可抑制结直肠癌细胞在体内的致瘤性。此外，京都基因与基因组百科全书（KEGG）富集分析表明，敲低PICALM导致丝裂原活化蛋白激酶（MAPK）信号通路富集。用MAPK抑制剂处理结直肠癌细胞可逆转PICALM过表达对增殖和凋亡的影响。此外，PICALM的过表达上调了ERK1/2（p-ERK1/2）、MEK1/2（p-MEK1/2）、p38（p-p38）和JNK（p-JNK）的蛋白水平，而MAPK抑制剂处理可部分缓解这些影响。
总之，本研究提出了新的发现，即PICALM通过ERK/MAPK信号通路促进结直肠癌进展，这使其作为一个有前景的治疗靶点的临床应用更受关注。
