Cervical Cancer Growth Is Regulated by a c-ABL-PLK1 Signaling Axis
Cervical Cancer Growth Is Regulated by a c-ABL-PLK1 Signaling Axis
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宫颈癌的生长受 c-ABL-PLK1 信号轴调节
DOI：
10.1158/0008-5472.can-16-1378
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发表时间：
2017-03-01
期刊：
影响因子：
11.2
通讯作者：
Pei, Huadong
中科院分区：
文献类型：
--
作者：
Yang, Xu;Chen, Gang;Pei, Huadong
非受体酪氨酸激酶c-ABL控制细胞生长，但其在实体瘤中的作用尚不完全清楚。在此，我们报道了Polo样激酶PLK1，一种重要的有丝分裂激酶调节因子，是c-ABL在调节宫颈癌生长中的重要下游效应因子。C-ABL与PLK1相互作用并磷酸化。C-ABL对PLK1的磷酸化抑制了PLK1的泛素化和降解，增强了PLK1的活性，导致细胞周期进展和肿瘤生长。C-ABL和PLK1在宫颈癌中均有过表达。值得注意的是，PLK1酪氨酸磷酸化与宫颈癌患者的生存相关。在人宫颈癌小鼠移植模型中，c-ABL和PLK1抑制剂联合治疗产生了抑制肿瘤生长的相加效应。我们的发现强调了c-ABL-PLK1轴作为一种新的宫颈癌预后标志物和治疗靶点。(C)2016年AACR。
The nonreceptor tyrosine kinase c-ABL controls cell growth but its contributions in solid tumors are not fully understood. Here we report that the Polo-like kinase PLK1, an essential mitotic kinase regulator, is an important downstream effector of c-ABL in regulating the growth of cervical cancer. c-ABL interacted with and phosphorylated PLK1. Phosphorylation of PLK1 by c-ABL inhibited PLK1 ubiquitination and degradation and enhanced its activity, leading to cell-cycle progression and tumor growth. Both c-ABL and PLK1 were overexpressed in cervical carcinoma. Notably, PLK1 tyrosine phosphorylation correlated with patient survival in cervical cancer. In a murine xenograft model of human cervical cancer, combination treatment with c-ABL and PLK1 inhibitors yielded additive effects on tumor growth inhibition. Our findings highlight the c-ABL-PLK1 axis as a novel prognostic marker and treatment target for human cervical cancers. (C) 2016 AACR.