Downregulation of MMSET impairs breast cancer proliferation and metastasis through inhibiting Wnt/β-catenin signaling
Open Access
- 1 March 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in OncoTargets and Therapy
- Vol. ume 12, 1965-1977
- https://doi.org/10.2147/ott.s196430
Abstract
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
This publication has 26 references indexed in Scilit:
- Histone Methyltransferase NSD2/MMSET Mediates Constitutive NF-κB Signaling for Cancer Cell Proliferation, Survival, and Tumor Growth via a Feed-Forward LoopMolecular and Cellular Biology, 2012
- The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial–mesenchymal transition and invasive properties of prostate cancerOncogene, 2012
- NSD2 Links Dimethylation of Histone H3 at Lysine 36 to Oncogenic ProgrammingMolecular Cell, 2011
- MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sitesNature, 2011
- The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the SubstrateOnline Journal of Public Health Informatics, 2009
- MMSET is overexpressed in cancers: Link with tumor aggressivenessBiochemical and Biophysical Research Communications, 2009
- Signature biomarkers in Crohn's disease: toward a molecular classificationMucosal Immunology, 2008
- The multiple myeloma–associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicityBlood, 2008
- Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myelomaBritish Journal of Haematology, 2005
- Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patientsBlood, 2005