Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of bladder cancer invasion.
Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of bladder cancer invasion.
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雷帕霉素复合物2（MTORC2）的哺乳动物靶标是膀胱癌入侵的关键决定因素。
DOI：
10.1371/journal.pone.0081081
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hansel DE
中科院分区：
文献类型：
--
作者：
Gupta S;Hau AM;Beach JR;Harwalker J;Mantuano E;Gonias SL;Egelhoff TT;Hansel DE
膀胱癌是美国男性癌症的第四大常见原因。侵袭性行为是预后的主要决定因素。在这项研究中，我们发现雷帕霉素复合体2的哺乳动物靶点(MTORC2)是膀胱癌细胞迁移和侵袭的中心调节因子。MTORC2活性通过AKT中Ser473的磷酸化程度进行评估，并被确定在浸润性膀胱癌标本中比非浸润性膀胱癌标本高约5倍。永生化恶性膀胱细胞系UMUC-3、J82和T24的mTORC2活性高于良性膀胱乳头状瘤细胞系RT4和正常尿路上皮细胞系HU1。恶性膀胱癌细胞在穿孔和剥离实验中也表现出更多的迁移，增加了对基质的侵袭，并增加了侵袭人膀胱标本的能力。作为mTORC2的关键成分，Rictor的基因沉默在很大程度上抑制了膀胱癌细胞的迁移和侵袭。伴随而来的是rac1活性和帕西林磷酸化的显著降低。这些研究确定mTORC2是中和膀胱癌侵袭的主要靶点。
Bladder cancer is the fourth most common cause of cancer in males in the United States. Invasive behavior is a major determinant of prognosis. In this study, we identified mammalian target of rapamycin complex 2 (mTORC2) as a central regulator of bladder cancer cell migration and invasion. mTORC2 activity was assessed by the extent of phosphorylation of Ser473 in AKT and determined to be approximately 5-fold higher in specimens of invasive human bladder cancer as opposed to non-invasive human bladder cancer. The immortalized malignant bladder cell lines, UMUC-3, J82 and T24 demonstrated higher baseline mTORC2 activity relative to the benign bladder papilloma-derived cell line RT4 and the normal urothelial cell line HU1. The malignant bladder cancer cells also demonstrated increased migration in transwell and denudation assays, increased invasion of matrigel, and increased capacity to invade human bladder specimens. Gene silencing of rictor, a critical component of mTORC2, substantially inhibited bladder cancer cell migration and invasion. This was accompanied by a significant decrease in Rac1 activation and paxillin phosphorylation. These studies identify mTORC2 as a major target for neutralizing bladder cancer invasion.
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影响因子：
11.2
作者：
Sos ML;Koker M;Weir BA;Heynck S;Rabinovsky R;Zander T;Seeger JM;Weiss J;Fischer F;Frommolt P;Michel K;Peifer M;Mermel C;Girard L;Peyton M;Gazdar AF;Minna JD;Garraway LA;Kashkar H;Pao W;Meyerson M;Thomas RK
通讯作者：
Thomas RK
影响因子：
3.3
作者：
Breckenridge, Mark T.;Dulyaninova, Natalya G.;Egelhoff, Thomas T.
通讯作者：
Egelhoff, Thomas T.
影响因子：
6
作者：
Hansel, Donna E.;Platt, Eric;Eng, Charis
通讯作者：
Eng, Charis
影响因子：
8
作者：
Gildea, JJ;Herlevsen, M;Theodorescu, D
通讯作者：
Theodorescu, D
影响因子：
4.8
作者：
Gan, Xiaoqing;Wang, Jiyong;Wu, Dianqing
通讯作者：
Wu, Dianqing