Jazf1 promotes prostate cancer progression by activating JNK/Slug

// Yonghun Sung 1, * , Song Park 1, 2, * , Si Jun Park 1, * , Jain Jeong 1 , Minjee Choi 1 , Jinhee Lee 1 , Wookbong Kwon 1 , Soyoung Jang 1 , Mee-Hyun Lee 3 , Dong Joon Kim 3 , Kangdong Liu 3 , Sung-Hyun Kim 3 , Jae-Ho Lee 4 , Yun-Sok Ha 5 , Tae Gyun Kwon 5 , Sanggyu Lee 1 , Zigang Dong 6 , Zae Young Ryoo 1 and Myoung Ok Kim 7 1 School of Life Science, BK21 Plus KNU Creative Bio Research Group, College of Natural Sciences, Kyungpook National University, Buk-ku, Daegu, Republic of Korea 2 Core Protein Resources Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea 3 China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China 4 Department of Anatomy, Keimyung University School of Medicine, Dalseo-gu, Daegu, Republic of Korea 5 Department of Urology, Kyungpook National University Medical Center, Buk-gu, Daegu, Korea 6 The Hormel Institute, University of Minnesota, NE, Austin, Minnesota, USA 7 The School of Animal BT Science, Kyungpook National University, Sangju-si, Gyeongsangbuk-do, Korea * These authors contributed equally to this work Correspondence to: Myoung Ok Kim, email: ok4325@knu.ac.kr Zae Young Ryoo, email: jaewoong64@hanmail.net Keywords: Jazf1; prostate cancer; metastasis; JNK; slug Received: July 08, 2017      Accepted: November 14, 2017      Published: December 12, 2017 ABSTRACT Juxtaposed with another zinc finger protein 1 (Jazf1) is a zinc finger protein and is known to affect both prostate cancer and type 2 diabetes. Jazf1 inhibits testicular nuclear receptor 4 (TR4) activation through protein-protein interaction, which results in weight loss and alleviates diabetes. However, the role of Jazf1 in prostate cancer is still poorly understood. Hence, we investigated whether the expression of Jazf1 is associated with prostate cancer progression. We confirmed the upregulation of Jazf1 expression in human prostate tissue samples. In addition, using Jazf1 overexpressing prostate cancer cell lines, DU145 and LNCaP, we found Jazf1 promoted cell proliferation and colony formation ability. We also observed that Jazf1 dramatically enhanced cell migration and invasion in transwell assays. Additionally, we checked the upregulation of vimentin and downregulation of E-cadherin expression in Jazf1-overexpressing DU145 and LNCaP cells. Moreover, we found that Slug, which is known to be regulated by JNK/c-Jun phosphorylation, was upregulated in the microarray analysis of two prostate cancer cell lines. Jazf1 promotes the phosphorylation of JNK/c-Jun, likely promoting cell proliferation and invasion through Slug. In a xenograft model, tumors overexpressing Jazf1 were larger than control tumors, and tumors with decreased Jazf1 were smaller. These data indicated that Jazf1 enhances prostate cancer progression and metastasis via regulating JNK/Slug signaling. Taken together, these results suggest that Jazf1 plays an important role in both androgen dependent and independent prostate cancer.