Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination.
Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination.
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通过抑制 USP14 介导的雄激素受体去泛素化来诱导雄激素受体阳性人乳腺癌细胞的生长停滞和凋亡
DOI：
10.1038/s41388-017-0069-z
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发表时间：
2018-04
期刊：
影响因子：
8
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Liao Y;Xia X;Liu N;Cai J;Guo Z;Li Y;Jiang L;Dou QP;Tang D;Huang H;Liu J
众所周知，雄激素受体(AR)在前列腺癌的发生发展中起着至关重要的作用。也有研究证明，AR在超过60%的乳腺肿瘤中表达，促进雌激素受体阴性(ER-)/AR阳性(AR+)乳腺癌细胞的生长。因此，AR可能成为AR阳性/ER阴性乳腺癌患者的潜在治疗靶点。在此之前，我们曾报道在前列腺癌细胞中，蛋白酶体相关的去泛素酶泛素特异蛋白酶14(USP14)通过去除泛素链来稳定AR蛋白水平。在本研究中，我们研究了USP14下调或抑制乳腺癌细胞后USP14-AR蛋白的相互作用和细胞增殖状态，结果支持了靶向USP14是治疗AR反应性乳腺癌的一种新策略的结论。我们发现，抑制USP14加速了K48泛素化和蛋白酶体介导的AR蛋白的降解。此外，USP14的基因和药物抑制都通过阻断G0/G1向S的转变和诱导细胞凋亡来显著抑制AR反应性乳腺癌细胞的增殖。此外，AR的过度表达抑制了USP14抑制诱导的事件，提示USP14的AR去泛素化对乳腺癌的生长至关重要，USP14抑制是治疗AR阳性乳腺癌的一种可能的策略。
It has been well known that androgen receptor (AR) is critical to prostate cancer development and progression. It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER–)/AR-positive (AR+) breast cancer cells. Thus, AR might be a potential therapeutic target for AR-positive/ER-negative breast cancer patients. Previously we reported that in prostate cancer cells proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level by removing its ubiquitin chain. In the current study, we studied the USP14-AR protein interaction and cell proliferation status after USP14 reduction or inhibition in breast cancer cells, and our results support the conclusion that targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome-mediated degradation of AR protein. Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G0/G1 to S phase transition and inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition-induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR-positive breast cancer.
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影响因子：
8
作者：
Guedj, M.;Marisa, L.;de Reynies, A.;Orsetti, B.;Schiappa, R.;Bibeau, F.;MacGrogan, G.;Lerebours, F.;Finetti, P.;Longy, M.;Bertheau, P.;Bertrand, F.;Bonnet, F.;Martin, A. L.;Feugeas, J. P.;Bieche, I.;Lehmann-Che, J.;Lidereau, R.;Birnbaum, D.;Bertucci, F.;de The, H.;Theillet, C.
通讯作者：
Theillet, C.
影响因子：
14.9
作者：
Draker R;Sarcinella E;Cheung P
通讯作者：
Cheung P
影响因子：
64.8
作者：
通讯作者：
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L-肉碱是一种内源性 HDAC 抑制剂，可选择性抑制体内和体外癌细胞生长
影响因子：
3.7
作者：
Huang H;Liu N;Guo H;Liao S;Li X;Yang C;Liu S;Song W;Liu C;Guan L;Li B;Xu L;Zhang C;Wang X;Dou QP;Liu J
通讯作者：
Liu J
影响因子：
11.4
作者：
Lin, HK;Wang, L;Chang, CS
通讯作者：
Chang, CS