The role of SH3RF2 in lung squamous cell carcinoma and M2 polarization: insights into LZTS2 ubiquitination

Background: Although the treatment of lung cancer has been well developed, the survival rate for lung squamous cell carcinoma (LUSC) is still low. It is meaningful to explore new molecular targets and develop new treatment strategies. SH3RF2 is an E3 ubiquitin ligase containing 3 SH3 domains and has not been reported in LUSC. Results: SH3RF2 promoted the proliferation of LUSC cells, and the nuclear translocation of β-catenin, increased Arg-1, CD163 and IL-10 RNA levels and the proportion of CD206+ cells in M0 THP-1 cells, and enhanced the migration and invasion of M0 THP-1 cells. ICG-001 alleviated the above effects of SH3RF2 on M0 THP-1 cell. In vivo tumorigenesis experiments found that SH3RF2 promoted tumor growth and increased the proportion of M2 cells. IP found that SH3RF2 interacted with LZTS2 and regulated the ubiquitination of LZTS2 with RING domain. LZTS2 overexpression reduced the nuclear translocation of β-catenin, cell migration and invasion, and M2 polarization promoted by SH3RF2 overexpression. The combination of SH3RF2 overexpression and radiotherapy inhibited the growth of tumor. Conclusions: This study elucidates the cancer-promoting role of SH3RF2, its positive effect on M2 polarization, and its relationship with LZTS2 and β-catenin. It provides new candidate molecular targets for the treatment of LUSC.