KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.
KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.
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KMT2A通过靶向hTERT信号通路促进黑色素瘤细胞生长
DOI：
10.1038/cddis.2017.285
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发表时间：
2017-07-20
影响因子：
9
通讯作者：
Deng W
中科院分区：
文献类型：
--
作者：
Zhang C;Song C;Liu T;Tang R;Chen M;Gao F;Xiao B;Qin G;Shi F;Li W;Li Y;Fu X;Shi D;Xiao X;Kang L;Huang W;Wu X;Tang B;Deng W
Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma.
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影响因子：
4.1
作者：
Abel, Haley J.;Al-Kateb, Hussam;Duncavage, Eric J.
通讯作者：
Duncavage, Eric J.
影响因子：
3.9
作者：
Basu N;Skinner HG;Litzelman K;Vanderboom R;Baichoo E;Boardman LA
通讯作者：
Boardman LA
影响因子：
82.9
作者：
Chen, Chun-Wei;Koche, Richard P.;Sinha, Amit U.;Deshpande, Aniruddha J.;Zhu, Nan;Eng, Rowena;Doench, John G.;Xu, Haiming;Chu, Scott H.;Qi, Jun;Wang, Xi;Delaney, Christopher;Bernt, Kathrin M.;Root, David E.;Hahn, William C.;Bradner, James E.;Armstrong, Scott A.
通讯作者：
Armstrong, Scott A.
DOI：
10.1126/science.1229259
发表时间：
2013-02-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huang FW;Hodis E;Xu MJ;Kryukov GV;Chin L;Garraway LA
通讯作者：
Garraway LA
影响因子：
3.5
作者：
Daniel M;Peek GW;Tollefsbol TO
通讯作者：
Tollefsbol TO