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 exists 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.

Human sperm-associated antigen 4 (SPAG4), as a member of the cancer-testis antigen(CTA) family, is considered to be a potential cancer marker. However, It is not known whether SPAG4 functions in the tumor immune microenvironment through some common mechanism. Here, we explored the oncogenic role of SPAG4 in 33 human tumors based on TCGA and GEO databases using web-based tools such as TIMER2.0, GEPIA2, TISIDE, ROC plotter, TIDE, and Western Blot experiments. The results showed that SPAG4 was highly expressed in 21 tumors and predicted a poor clinical prognosis in most tumors. Moreover, SPAG4 has an important role in the tumor microenvironment and is likely to be involved in the regulation of the immune microenvironment. Most importantly, SPAG4 expression was significantly associated with drug resistance and immune checkpoint blockade therapy in tumor patients, and could potentially regulate the occurrence of immune escape. In conclusion, our study suggests that SPAG4 is an immune oncogenic molecule that can be used as a biomarker for cancer detection, prognosis, treatment design and follow-up.