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ZNF507 affects TGF-β signaling via TGFBR1 and MAP3K8 activation in the progression of prostate cancer to an aggressive state

Title
ZNF507 affects TGF-β signaling via TGFBR1 and MAP3K8 activation in the progression of prostate cancer to an aggressive state
Authors
Kwon, WookbongChoi, Seong-KyoonKim, DaehwanKim, Hyeon-GyeomPark, Jin-KyuHan, Jee EunCho, Gil-JaeYun, SunghoYu, WookyungHan, Se-HyeonHa, Yun-SokLee, Jun NyungKwon, Tae GyunCho, Dong-HyungYi, Jun-KooKim, Myoung OkRyoo, Zae YoungPark, Song
DGIST Authors
Kwon, Wookbong; Choi, Seong-Kyoon; Kim, Daehwan; Kim, Hyeon-Gyeom; Park, Jin-Kyu; Han, Jee Eun; Cho, Gil-Jae; Yun, Sungho; Yu, Wookyung; Han, Se-Hyeon; Ha, Yun-Sok; Lee, Jun Nyung; Kwon, Tae Gyun; Cho, Dong-Hyung; Yi, Jun-Koo; Kim, Myoung Ok; Ryoo, Zae Young; Park, Song
Issue Date
2021-09
Citation
Journal of Experimental & Clinical Cancer Research, 40(1)
Type
Article
Author Keywords
Prostate cancerMetastasismCRPCZNF507TGF-beta signal
Keywords
CARCINOMA-CELL LINENEUROENDOCRINE DIFFERENTIATIONEXPRESSIONINFLAMMATIONMECHANISMSFURINLANDSCAPEGROWTHTUMORS
ISSN
1756-9966
Abstract
Background: The progression of prostate cancer (PC) to the highly aggressive metastatic castration-resistant prostate cancer (mCRPC) or neuroendocrine prostate cancer (NEPC) is a fatal condition and the underlying molecular mechanisms are poorly understood. Here, we identified the novel transcriptional factor ZNF507 as a key mediator in the progression of PC to an aggressive state. Methods: We analyzed ZNF507 expression in the data from various human PC database and high-grade PC patient samples. By establishment of ZNF507 knockdown and overexpression human PC cell lines, we assessed in vitro PC phenotype changes including cell proliferation, survival, migration and invasion. By performing microarray with ZNF507 knockdown PC cells, we profiled the gene clusters affected by ZNF507 knockdown. Moreover, ZNF507 regulated key signal was evaluated by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Finally, we performed xenograft and in vivo metastasis assay to confirm the effect of ZNF507 knockdown in PC cells. Results: We found that ZNF507 expression was increased, particularly in the highly graded PC. ZNF507 was also found to be associated with metastatic PC of a high grade. Loss- or gain-of-function–based analysis revealed that ZNF507 promotes the growth, survival, proliferation, and metastatic properties of PC (e.g., epithelial-mesenchymal transition) by upregulating TGF-β signaling. Profiling of gene clusters affected by ZNF507 knockdown revealed that ZNF507 positively regulated the transcription of TGFBR1, MAP3K8, and FURIN, which in turn promoted the progression of PC to highly metastatic and aggressive state. Conclusions: Our findings suggest that ZNF507 is a novel key regulator of TGF-β signaling in the progression of malignant PC and could be a promising target for studying the development of advanced metastatic PCs. © 2021, The Author(s).
URI
http://hdl.handle.net/20.500.11750/15343
DOI
10.1186/s13046-021-02094-3
Publisher
Springer Science and Business Media LLC
Related Researcher
  • Author Yu, Wookyung Laboratory of Protein Biophysics
  • Research Interests protein biophysics; protein folding; protein dynamics and conformational change
Files:
Collection:
Division of Biotechnology1. Journal Articles
Department of Brain SciencesLaboratory of Protein Biophysics1. Journal Articles


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