SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells

Abstract

// Jungsug Gwak 1 , Jee Yoon Shin 1 , Kwanghyun Lee 1 , Soon Ki Hong 1 , Sangtaek Oh 2 , Sung-Ho Goh 3 , Won Sun Kim 1 , Bong Gun Ju 1 1 Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea 2 Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea 3 Research Institute, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea Correspondence to: Bong Gun Ju, email: bgju@sogang.ac.kr Keywords: prostate cancer, metastasis, SFMBT2, gene regulation Received: December 28, 2015      Accepted: June 04, 2016      Published: June 21, 2016 ABSTRACT Metastatic prostate cancer is the leading cause of morbidity and mortality in men. In this study, we found that expression level of SFMBT2 is altered during prostate cancer progression and has been associated with the migration and invasion of prostate cancer cells. The expression level of SFMBT2 is high in poorly metastatic prostate cancer cells compared to highly metastatic prostate cancer cells. We also found that SFMBT2 knockdown elevates MMP-2, MMP-3, MMP-9, and MMP-26 expression, leading to increased cell migration and invasion in LNCaP and VCaP cells. SFMBT2 interacts with YY1, RNF2, N-CoR and HDAC1/3, as well as repressive histone marks such as H3K9me2, H4K20me2, and H2AK119Ub which are associated with transcriptional repression. In addition, SFMBT2 knockdown decreased KAI1 gene expression through up-regulation of N-CoR gene expression. Expression of SFMBT2 in prostate cancer was strongly associated with clinicopathological features. Patients having higher Gleason score (≥ 8) had substantially lower SFMBT2 expression than patients with lower Gleason score. Moreover, tail vein or intraprostatic injection of SFMBT2 knockdown LNCaP cells induced metastasis. Taken together, our findings suggest that regulation of SFMBT2 may provide a new therapeutic strategy to control prostate cancer metastasis as well as being a potential biomarker of metastatic prostate cancer.