Reciprocal negative feedback regulation ofATF6α andPTEN promotes prostate cancer progression
Reciprocal negative feedback regulation ofATF6α andPTEN promotes prostate cancer progression
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DOI：
10.1007/s00018-023-04940-3
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Bo Han
中科院分区：
文献类型：
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作者：
Tingting Feng;Ru Zhao;Hanwen Zhang;Feifei Sun;Jing Hu;Meng Wang;Mei Qi;Ling Liu;Lin Gao;Yabo Xiao;Junhui Zhen;Weiwen Chen;Lin Wang;Bo Han
Phosphatase and tensin homolog (PTEN) loss tightly correlates with prostate cancer (PCa) progression and metastasis. .Inactivation of PTEN leads to abnormal activation of PI3K/AKT pathway. However, results from clinical trials with AKT .inhibitors in PCa have been largely disappointing. Identifcation of novel regulators of PTEN in PTEN-dysfunctional PCa .is urgently needed. Here we demonstrated that the expression level of PTEN is inversely correlated with the signature score .of unfolded protein response (UPR) in PCa. Importantly, PTEN suppresses the activity of ATF6α, via interacting to dephosphorylate ATF6α and consequently inhibiting its nuclear translocation. Conversely, ATF6α promotes the ubiquitination .and degradation of PTEN by inducing CHIP expression. Thus, ATF6α and PTEN forms a negative feedback loop during PCa .progression. Combination of ATF6α inhibitor with AKT inhibitor suppresses tumor cell proliferation and xenograft growth. .Importantly, this study highlighted ATF6α as a therapeutic vulnerability in PTEN dysfunctional PCa.
