反对负反调节ATF6α和PTEN促进前列腺癌的进展
Tingting Feng1, Ru Zhao1,2, Hanwen Zhang1
1The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.
Cellular and molecular life sciences : CMLS
|September 16, 2023
概括
酸酶和张素同类素 (PTEN) 的损失驱动前列腺癌 (PCa) 的进展. 这项研究揭示了PTEN和ATF6α之间的负反循环,确定ATF6α是PTEN功能障碍PCa的治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 前列腺癌 (PCa) 的进展和转移与酸酶和张素同类素 (PTEN) 的丧失有关.
- PTEN无活化激活PI3K/AKT通路,但AKT抑制剂在PCa临床试验中表现出有限的成功.
- 在PTEN-功能障碍的PCa中,对PTEN的新型调节剂有极大需求.
研究的目的:
- 研究PTEN与PCa.中未折叠蛋白反应 (UPR) 之间的关系.
- 阐明前列腺癌中PTEN和ATF6α之间的调节机制.
- 探索ATF6α作为PTEN缺乏PCa的潜在治疗点.
主要方法:
- 在PCa中,PTEN表达和UPR签名得分之间的相关性分析.
- 研究PTEN和ATF6α之间的相互作用,包括PTEN对ATF6α的脱化.
- 通过CHIP诱导评估ATF6α在PTEN降解中的作用.
- 在临床前模型中评估ATF6α和AKT抑制剂组合的疗效.
主要成果:
- 在PCa中,PTEN表达与UPR签名得分相反相关.
- PTEN去酸化并抑制ATF6α的核转移.
- 通过对CHIP进行上调调节,ATF6α促进了PTEN的泛化和降解.
- 在PCa进展中,ATF6α和PTEN之间存在负反循环.
- 联合ATF6α和AKT抑制抑制了瘤细胞的增殖和异种移植的生长.
结论:
- 在前列腺癌中,ATF6α和PTEN形成一个相互调节的循环.
- 向ATF6α代表了对PTEN功能障碍前列腺癌的有前途的治疗策略.
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