title: Regulation of CXCR4/AKT-signaling-induced cell invasion and tumor metastasis by RhoA, Rac-1, and Cdc42 in human esophageal cancer.
abstract: CXC chemokines and their cognate receptors have been implicated wildly in cancer pathogenesis. In the present study, we report a critical cause relationship between CXCR4 expression and tumorigenesis in the setting of human esophageal squamous cell carcinoma (ESCC). In ESCC cells, CXCR4 expression was significantly higher than in human esophageal epithelial cells (HEEC). Reduction of CXCR4 in ESCC cells reduced cell proliferation and invasion in vitro and tumor growth in vivo. Among the potential downstream targets of CXCR4-CXCL12 are RhoA, Rac-1, and Cdc42, which are likely to contribute to the invasiveness of ESCC cells. Finally, we found that CXCR4-CXCL12/AKT axis regulates RhoA, Rac-1, and Cdc42 to modulate cell invasion and tumor metastasis. Together, these results demonstrate a role for CXCR4 in ESCC metastasis and progression and suggest potential targets for therapeutic intervention.
authors.affiliation: Department of Thoracic Surgery, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin RD, Shanghai, 200032, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin RD, Shanghai, 200032, People's Republic of China.
authors.forename: Zongwu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Shanghai No.1 Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Guangyin
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin RD, Shanghai, 200032, People's Republic of China.
authors.forename: Fengkai
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin RD, Shanghai, 200032, People's Republic of China. lu.chunlai@zs-hospital.sh.cn.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin RD, Shanghai, 200032, People's Republic of China. ge.di@zs-hospital.sh.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Ge
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D054377:Chemokine CXCL12 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D051058:Oncogene Protein v-akt / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D020764:cdc42 GTP-Binding Protein / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C107953:RAC1 protein, human; D019718:Receptors, CXCR4; C066737:RHOA protein, human; D051058:Oncogene Protein v-akt; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: CXCR4; Chemokines; Esophageal neoplasms; Neoplasm metastasis; PI3K/AKT