WHSC1 promotes wnt/β-catenin signaling in a FoxM1-dependent manner facilitating proliferation, invasion and epithelial-mesenchymal transition in breast cancer

Abstract

Objectives: Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1) is highly expressed in various malignant tumors. We investigated the correlation and regulatory pathway of WHSC1 in the progression of breast cancer (BC).Methods: The expression and distribution of WHSC1 in the BC tissues and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining. Spearman correlation analysis demonstrated the correlation between WHSC1 high expression level and the clinical characteristics of BC patients. The effects of WHSC1 on the proliferation, apoptosis, migration and invasion of BC cells were analyzed by cell transfection, MTT, colony formation, scratch assay, and transwell. Furthermore, the expression of Forkhead box M1 (FoxM1) and the location of β-catenin were detected by qRT-PCR and western blot.Results: Firstly, WHSC1 expression was up-regulated in BC tissues and cell lines. The high expression of WHSC1 in BC is associated with the tumor size (p = 0.027), metastasis (p = 0.018) and pathological stages (p = 0.025) of the BC patients. The knockdown of WHSC1 inhibited the growth, proliferation migration, invasion and EMT of BC cell lines. Furthermore, WHSC1 could promote the expression of FoxM1 in BC cells and tissues. WHSC1 enhanced the expression of FoxM1, and promoted the nuclear localization of β-catenin, and thus activated the downstream genes expression of Wnt/β-catenin signaling pathway to regulate the development of BC.Conclusion: In summary, our study elucidates the correlation and specific regulatory mechanism between WHSC1 and the progression of BC, thus implying that WHSC1 may function as molecular diagnosis, prognosis and molecular targeted therapy of BC.