Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1

Yankang Cui; Chenkui Miao; Shouyong Liu; Jingyuan Tang; Jing Zhang; Hengtao Bu; Yuhao Wang; Chao Liang; Meiling Bao; Chao Hou; Jiajin Wu; Xiaochao Chen; Xiang Zhang; Zengjun Wang; Bianjiang Liu

doi:10.1016/j.omtn.2021.11.004

Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1

Mol Ther Nucleic Acids. 2021 Nov 10:26:1336-1350. doi: 10.1016/j.omtn.2021.11.004. eCollection 2021 Dec 3.

Authors

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
² Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
³ School of Chemistry and Chemical Engineering, Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
⁴ Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Abstract

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.

Keywords: COL15a1; EMT; MEF2A; clusterin; seminoma; testicular xenografts in situ.