TSPYL5 activates endoplasmic reticulum stress to inhibit cell proliferation, migration and invasion in colorectal cancer.

Testis‑specific protein Y‑encoded‑like 5 (TSPYL5), a member of the nucleosome assembly protein (NAP) superfamily, functions as a tumor suppressor in ovarian and lung cancer, yet its clinical significance and molecular mechanism in colorectal cancer (CRC) remain unclear. TSPYL5 expression was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. CRC cell lines HCT116 and HT29 were forced to overexpress TSPYL5 by transfection with pcDNA3.1‑TSPYL5. Cell proliferation, apoptosis, migration, and invasion were examined by EdU proliferation assays, flow cytometry, and Transwell assays, respectively. Endoplasmic reticulum stress (ERS) was examined by transmission electron microscopy. Western blot analyses were performed to assess the expression of ERS‑associated proteins. GEPIA database analysis showed that CRC patients had lower levels of TSPYL5 expression in their tumor tissues when compared with their para‑carcinoma tissues. In vitro experiments indicated that TSPYL5 overexpression significantly suppressed cell proliferation, migration, and invasion, and induced apoptosis and ERS in HCT116 and HT29 cells. Furthermore, the levels of caspase‑1, caspase‑3, Bax, ATF4, and CHOP protein expression were upregulated after TSPYL5 was overexpressed. In conclusion, our data suggest that TSPYL5 can activate an ERS response that suppresses the proliferation, migration, and invasion of tumor cells. This mechanism may represent a promising therapeutic strategy for CRC.