NMMHC-IIA-dependent nuclear location of CXCR4 promotes migration and invasion in renal cell carcinoma
NMMHC-IIA-dependent nuclear location of CXCR4 promotes migration and invasion in renal cell carcinoma
复制标题
CXCR4 依赖于 NMMHC-IIA 的核定位促进肾细胞癌的迁移和侵袭
DOI：
10.3892/or.2016.5082
复制
发表时间：
2016-11-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Linhui
中科院分区：
文献类型：
--
作者：
Xu, Zhipeng;Li, Peng;Wang, Linhui
趋化因子受体半胱氨酸(C)-X-C受体（CXCR4）是一种g蛋白偶联受体，在肾细胞癌（RCC）的远处转移中发挥重要作用。新出现的证据表明，CXCR4作为细胞膜受体易位到细胞核中，促进细胞迁移，并因此决定了几种类型恶性肿瘤的预后。然而，CXCR4核定位的生物学机制尚不清楚。在本研究中，我们通过RCC细胞系的点突变实验证实了假定的核定位序列（NLS） ‘146RPRK149’对CXCR4亚细胞定位和转移潜力的重要意义。重要的是，免疫沉淀后的质谱鉴定出非肌肉肌球蛋白重链- iia （NMMHC-IIA）是cxcr4相互作用蛋白。此外，blebbistatin对NMMHC-IIA的药物抑制抑制了CXCR4的核易位以及RCC细胞的转移能力。综上所述，本研究可能推动对CXCR4核功能和肿瘤转移机制的全面研究。
The chemokine receptor cysteine (C)-X-C receptor (CXCR4) is a G-protein-coupled receptor that exerts a vital role in distant metastasis of renal cell carcinoma (RCC). Emerging evidence demonstrates that CXCR4 as the cytomembrane receptor translocated into the nucleus to facilitate cell migration- and, therefore, determine the prognosis of several types of malignancies. However, the biological mechanism of nuclear location of CXCR4 remains unclear. In the present study, we confirmed the significant implications of the putative nuclear localization sequence (NLS) '146RPRK149' on CXCR4 subcellular localization and metastatic potential by point-mutation assay in RCC cell lines. Importantly, mass spectrum followed by immunoprecipitation identified non-muscle myosin heavy chain-IIA (NMMHC-IIA) as the CXCR4-interacting protein. Furthermore, pharmaceutical inhibition of NMMHC-IIA by blebbistatin dampened the nuclear translocation of CXCR4 as well as the metastatic capacity of RCC cells. In conclusion, the present study may drive the comprehensive progress toward elucidating the mechanism responsible for CXCR4 nuclear function and metastasis in tumors.