SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells
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Jungsug Gwak1, Jee Yoon Shin1, Kwanghyun Lee1, Soon Ki Hong1, Sangtaek Oh2, Sung-Ho Goh3, Won Sun Kim1, Bong Gun Ju1
1Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea
2Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea
3Research Institute, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea
Bong Gun Ju, email: [email protected]
Keywords: prostate cancer, metastasis, SFMBT2, gene regulation
Received: December 28, 2015 Accepted: June 04, 2016 Published: June 21, 2016
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.
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