LAUSR

Simple Summary Globally, colorectal cancer (CRC) is one of the most common malignant tumors, and the SUN protein family regulates the proliferation and migration of tumors. However, the biological function and mechanism of SUN5 in CRC are unclear. In this study, we found that SUN5 was highly expressed in CRC tissues and cells. Moreover, SUN5 promoted the proliferation and migration of CRC both in vitro and in vivo by cooperating with Nesprin2 to regulate the ERK pathway and interacting with Nup93 to promote the nuclear translocation of phosphorylated ERK1/2. Taken together, our findings provide novel insight into the role of SUN5 in CRC progression and imply that SUN5 might be a biomarker and therapeutic target for CRC patients. Abstract SUN5 was first identified as a nuclear envelope protein involved in spermatocyte division. We found that SUN5 was highly expressed in some cancers, but its function and mechanism in cancer development remain unclear. In the present study, we demonstrated that SUN5 was highly expressed in colorectal cancer (CRC) tissues and cells, as indicated by bioinformatics analysis, and SUN5 promoted cell proliferation and migration in vitro. Moreover, the overexpression of SUN5 upregulated phosphorylated ERK1/2 (pERK1/2), whereas the knockdown of SUN5 yielded the opposite results. PD0325901 decreased the level of pERK1/2 to inhibit cell proliferation and migration, which was partially reversed by SUN5 overexpression, indicating that drug resistance existed in patients with high SUN5 expression. The xenograft transplantation experiment showed that SUN5 accelerated tumor formation in vivo. Furthermore, we found that SUN5 regulated the ERK pathway via Nesprin2 mediation and promoted the nuclear translocation of pERK1/2 by interacting with Nup93. Thus, these findings indicated that highly expressed SUN5 promoted CRC proliferation and migration by regulating the ERK pathway, which may contribute to the clinical diagnosis and new treatment strategies for CRC.