CDC37L1 acts as a suppressor of migration and proliferation in gastric cancer by down-regulating CDK6

Abstract

The co-chaperone protein CDC37 (Cell division cycle 37) is well known to regulate multiple protein kinases and involved in tumor progression. However to date, little is known about its analogue CDC37L1 (Cell division cycle 37 like 1) in tumorigenesis. This study aimed to explore the expression and function of CDC37L1 in gastric cancer (GC). The immunohistochemical staining in a tissue microarray showed a weak expression of CDC37L1 in high grade GC tissues compared with low grade tissues. Consistently, data from online database analysis demonstrated that CDC37L1 level was decreased in stage 4 patients and low expression of CDC37L1 indicated a poor prognosis. Functional studies revealed that CDC37L1 could inhibit GC cell proliferation and migration in CCK8, EdU incorporation, colony formation and transwell assays. In the meantime, CDC37L1 also inhibited the tumorigenicity of GC cells in nude mice. Mechanistically, we found that CDC37L1 had an impact on CDK6 protein expression by western blotting. Palbociclib, a specific CDK4/6 inhibitor, was discovered to block the rapid growth phenotype of GC cells induced by CDC37L1 silencing. Taken together, these findings unveiled a tumor-suppressive role of CDC37L1 in GC, and CDK6 may act as a downstream effector in this process.