NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers.
NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers.
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DOI：
10.1016/j.ccr.2012.12.001
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发表时间：
2013-01-14
期刊：
影响因子：
50.3
通讯作者：
Zhan F
中科院分区：
文献类型：
--
作者：
Zhou W;Yang Y;Xia J;Wang H;Salama ME;Xiong W;Xu H;Shetty S;Chen T;Zeng Z;Shi L;Zangari M;Miles R;Bearss D;Tricot G;Zhan F
利用序列基因表达谱(GEP)样本，我们定义了一个与耐药相关的主要功能群，其中包含染色体不稳定(CIN)基因。一个CIN基因，特别是NEK2，与多种癌症的耐药性、快速复发和不良预后密切相关。在癌细胞中过表达NEK2可增强CIN、细胞增殖和耐药性，而通过NEK2 shRNA靶向NEK2克服了癌细胞的耐药性，并在体外和异种骨髓瘤小鼠模型中诱导细胞凋亡。NEK2的高表达主要通过激活外排泵诱导耐药。因此，NEK2代表了癌症耐药和预后不良的强有力的预测因子，并可能成为癌症治疗的重要靶点。
Using sequential gene expression profiling (GEP) samples, we defined a major functional group related to drug resistance that contains chromosomal instability (CIN) genes. One CIN gene in particular, NEK2, was highly correlated with drug resistance, rapid relapse, and poor outcome in multiple cancers. Over-expressing NEK2 in cancer cells resulted in enhanced CIN, cell proliferation and drug resistance, while targeting NEK2 by NEK2 shRNA overcame cancer cell drug resistance and induced apoptosis in vitro and in a xenograft myeloma mouse model. High expression of NEK2 induced drug resistance mainly through activation of the efflux pumps. Thus, NEK2 represents a strong predictor for drug resistance and poor prognosis in cancer and could be an important target for cancer therapy.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
20.3
作者：
Avet-Loiseau, H;Facon, T;Bataille, R
通讯作者：
Bataille, R
DOI：
10.1073/pnas.94.6.2168
发表时间：
1997-03-18
影响因子：
11.1
作者：
Kwon, YG;Lee, SY;Nairn, AC
通讯作者：
Nairn, AC
影响因子：
20.3
作者：
Bergsagel, PL;Kuehl, WM;Shaughnessy, J
通讯作者：
Shaughnessy, J