ORP8 inhibits renal cell carcinoma progression by accelerating Stathmin1 degradation and microtubule polymerization.
ORP8 inhibits renal cell carcinoma progression by accelerating Stathmin1 degradation and microtubule polymerization.
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DOI：
10.1016/j.yexcr.2023.113601
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发表时间：
2023-04
影响因子：
3.7
通讯作者：
Lin Zhang;Q. Pan;Yi Wu;Peng Zhang;Shibao Li;Yuting Xu;Danhua Li;Maojin Zheng;D. Pei
中科院分区：
文献类型：
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作者：
Lin Zhang;Q. Pan;Yi Wu;Peng Zhang;Shibao Li;Yuting Xu;Danhua Li;Maojin Zheng;D. Pei
据报道，ORP8可抑制各种恶性肿瘤的肿瘤进展。然而，ORP8在肾细胞癌（RCC）中的功能和机制尚不清楚。功能分析证实，ORP8抑制RCC细胞的生长、迁移、侵袭和转移。从机制上讲，ORP8通过加速泛素介导的蛋白酶体降解来减弱Stathmin 1的表达，并导致微管聚合的增加。最后，ORP8敲低部分挽救了微管聚合，以及紫杉醇诱导的侵袭性细胞表型。我们的研究结果阐明了ORP8通过增加Stathmin 1的降解和微管聚合来抑制RCC的恶性进展，从而表明ORP8可能是治疗RCC的新靶点。
ORP8 has been reported to suppress tumor progression in various malignancies. However, the functions and underlying mechanisms of ORP8 are still unknown in renal cell carcinoma (RCC).Here, decreased expression of ORP8 was detected in RCC tissues and cell lines. Functional assays verified that ORP8 suppressed RCC cell growth, migration, invasion, and metastasis. Mechanistically, ORP8 attenuated Stathmin1 expression by accelerating ubiquitin-mediated proteasomal degradation and led to an increase in microtubule polymerization. Lastly, ORP8 knockdown partly rescued microtubule polymerization, as well as aggressive cell phenotypes induced by paclitaxel. Our findings elucidated that ORP8 suppressed the malignant progression of RCC by increasing Stathmin1 degradation and microtubule polymerization, thus suggesting that ORP8 might be a novel target for the treatment of RCC.