title: NMMHC-IIA-dependent nuclear location of CXCR4 promotes migration and invasion in renal cell carcinoma.
abstract: 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) '146RPRK149̓ 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.
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Health Contingent, No. 71210 Unit of People's Liberation Army, Yantai, Shantong 264001, P.R. China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D006576:Heterocyclic Compounds, 4 or More Rings; D006801:Humans; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D017354:Point Mutation; D019718:Receptors, CXCR4 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C527276:CXCR4 protein, human; D006576:Heterocyclic Compounds, 4 or More Rings; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D019718:Receptors, CXCR4; C472645:blebbistatin; D018995:Myosin Heavy Chains