title: XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer.
abstract: Bone metastasis occurs in approximately 30-40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis.
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tielong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: brilliant212@163.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: cnspineyang@163.com.
authors.forename: Xinghai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: jianruxiao83@163.com.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D019744:Chemokines, C / Q000502:physiology; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D019744:Chemokines, C; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C092390:XCL1 protein, human; C091671:XCR1 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Bone metastasis; Cell migration; Cell proliferation; JAK2/STAT3 pathway; Non-small cell lung cancer (NSCLC); XCR1