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| 題名: | Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer |
| 作者: | 林雍偉
Yung-Wei Lin, Yu-Ching Wen, Chih-Ying Chu, Min-Che Tung, Yi-Chieh Yang, Kuo-Tai Hua, Ke-Fan Pan, Michael Hsiao, Wei-Jiunn Lee & Ming-Hsien Chien |
| 貢獻者: | 國際醫學研究博士學位學程 |
| 日期: | 2020-07 |
| 上傳時間: | 2025-03-27 11:44:55 (UTC+8) |
| 摘要: | Abstract
N-α-Acetyltransferase 10 protein (Naa10p) was reported to be an oncoprotein in androgen-dependent prostate cancer (PCa; ADPC) through binding and increasing transcriptional activity of the androgen receptor (AR). PCa usually progresses from an androgen-dependent to an androgen-independent stage, leading to an increase in the metastatic potential and an incurable malignancy. At present, the role of Naa10p in androgen-independent prostate cancer (AIPC) remains unclear. In this study, in silico and immunohistochemistry analyses showed that Naa10 transcripts or the Naa10p protein were more highly expressed in primary and metastatic PCa cancer tissues compared to adjacent normal tissues and non-metastatic cancer tissues, respectively. Knockdown and overexpression of Naa10p in AIPC cells (DU145 and PC-3M), respectively, led to decreased and increased cell clonogenic and invasive abilities in vitro as well as tumor growth and metastasis in AIPC xenografts. From the protease array screening, we identified a disintegrin and metalloprotease 9 (ADAM9) as a potential target of Naa10p, which was responsible for the Naa10p-induced invasion of AIPC cells. Naa10p can form a complex with ADAM9 to maintain ADAM9 protein stability and promote AIPC’s invasive ability which were independent of its acetyltransferase activity. In contrast to the Naa10p-ADAM9 axis, ADAM9 exerted positive feedback regulation on Naa10p to modulate progression of AIPC in vitro and in vivo. Taken together, for the first time, our results reveal a novel cross-talk between Naa10p and ADAM9 in regulating the progression of AIPC. Disruption of Naa10p–ADAM9 interactions may be a potential intervention for AIPC therapy. |
| 關聯: | Cell Death & Disease volume 11, Article number: 591 (2020) |
| 描述: | 【112-3 升等】臺北醫學大學教師升等專門著作
職別：專任
送審等級：副教授
著作送審 |
| 資料類型: | article |
| 顯示於類別: | [教師升等送審著作] 112
[國際醫學研究碩博士學位學程] 期刊論文
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