LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells.

Leucine‑rich repeat‑containing protein 59 (LRRC59), a 244‑amino‑acid endoplasmic reticulum membrane protein, is implicated in the tumorigenesis of multiple malignancies. However, its functional significance in colorectal cancer (CRC) remains poorly understood. In the present study, LRRC59 expression in CRC tissues was evaluated using immunohistochemistry and western blotting. Colony formation, Cell Counting Kit‑8, wound healing and Transwell assays, in in vivo xenograft models, were used to evaluate the effect of LRRC59 on CRC progression. Apoptosis was analyzed using flow cytometry and western blotting. The interaction between LRRC59 and the protein kinase RNA‑like endoplasmic reticulum kinase (PERK) pathway was verified using the starBase database and western blotting. It was found that LRRC59 expression was significantly higher in CRC tissues than in normal tissues. LRRC59 knockdown in HCT116 and LoVo cells inhibited proliferation, migration and invasion and promoted apoptosis, and the PERK pathway was significantly activated. In vivo subcutaneous tumorigenesis assays corroborated these in vitro findings. Treatment with a PERK pathway‑specific inhibitor reduced the apoptosis of HCT116 and LoVo cells with LRRC59 knockdown. These findings suggest that LRRC59 is not only significantly upregulated in CRC but also mechanistically drives tumor progression by coordinating pro‑oncogenic processes, including enhanced proliferation, migration and invasion. Importantly, mechanistic evidence was provided that LRRC59 inhibits apoptosis by suppressing the PERK signaling axis, identifying this molecule a target in the development of CRC therapeutic strategies.