OncoTargets and Therapy (Mar 2019)
Downregulation of MMSET impairs breast cancer proliferation and metastasis through inhibiting Wnt/β-catenin signaling
Abstract
Xiaohui Zhao,1,* Tian Xie,1,* Wenhui Zhao,2,3,* Wanhua Cai,1 Xiaobo Su1 1GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China; 2State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Cancer Center, Guangzhou 510060, China; 3Juancheng People’s Hospital, Juancheng 274600, China *These authors contributed equally to this work Background: Recently, the biggest challenge in the treatment of breast cancer is the metastasis of breast cancer cells. Multiple myeloma SET protein (MMSET), a histone lysine methyltransferase, overexpressed in various human cancers, was reported to be associated with carcinogenesis of human cancers. Methods: Expression of MMSET in breast cancer cell lines and tissues was quantified by real-time PCR and Western blotting. Immunohistochemistry was employed to analyze MMSET expression in 163 clinicopathologically characterized breast cancer cases. Cell functional assays such as MTT assay, colony formation, BrdU assay, flow cytometry, wound healing, Transwell assay, and 3D culture were used to investigate the effect of MMSET in the development and metastasis of human breast cancer. Effects of MMSET on Wnt/β-catenin signaling pathway were further studied by using Western blotting analysis. Results: Our results showed that MMSET expression was markedly overexpressed in breast cancer cells and clinical specimens and was significantly correlated with patients’ clinicopathologic characteristics and prognosis. Moreover, silencing endogenous MMSET significantly inhibited the proliferation, migration, and metastasis of breast cancer cells through inhibiting the Wnt/β-catenin pathway. Conclusion: This study found that the downregulated expression of MMSET impaired proliferation and metastasis of human breast cancer through inhibiting Wnt/β-catenin signaling pathway. Notably, our results indicated that MMSET could be a useful biomarker for the prognosis of breast cancer. Keywords: multiple myeloma SET protein, carcinogenesis, patient’s clinicopathologic characteristics, prognosis, biomarker
