Jazf1 promotes prostate cancer progression by activating JNK/ Slug

Yonghun Sung, Song Park, Si Jun Park, Jain Jeong, Minjee Choi, Jinhee Lee, Wookbong Kwon, Soyoung Jang, Mee Hyun Lee, Dong Joon Kim, Kangdong Liu, Sung Hyun Kim, Jae Ho Lee, Yun Sok Ha, Tae Gyun Kwon, Sanggyu Lee, Zigang Dong, Zae Young Ryoo, Myoung Ok Kim

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)755-765
Number of pages11
JournalOncotarget
Volume9
Issue number1
DOIs
StatePublished - 2018

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B 4014686), (No. 2017R1A2B4007888), and (No. 2017R 1D1A1B03029234).

Keywords

  • JNK
  • Jazf1
  • Metastasis
  • Prostate cancer
  • Slug

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