Sohlh2 inhibits breast cancer cell proliferation by suppressing Wnt/β-catenin signaling pathway.

Sohlh2 belongs to the superfamily of basic helix-loop-helix (bhlh) transcription factors. Aberrant expression of bhlh transcription factors has been shown to be associated with multiple tumorigenesis. We previously identified that sohlh2 functioned as a tumor suppressor in ovarian cancer. Here, we examined the expression levels of sohlh2 in human breast cancer and its potential role in disease pathogenesis. The results of sohlh2 immunohistochemistry (IHC) and Western blot analysis demonstrated the decreased sohlh2 expression in breast cancer specimens as compared to adjacent noncancerous tissues. Through in vitro MTT, BrdU, colony formation and cell cycle assays and in vivo tumor xenograft studies, we showed that forced expression of sohlh2 led to a significant reduction in proliferation due to G1 arrest in vitro and tumorigenesis in nude mice. Conversely, silencing of sohlh2 enhanced breast cancer cell proliferation. Furthermore, we confirmed that sohlh2 inhibited breast cancer cell proliferation by suppressing the Wnt/β-catenin signaling pathway. APC was the direct target of sohlh2, and mediated the inhibitory activities of sohlh2 on Wnt/β-catenin signaling pathway. Thus, our data indicate that sohlh2 likely functions as a tumor suppressor in breast cancer that is mediated by repressing Wnt/β-catenin signaling pathway via upregulation of APC expression.