title: Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer.
abstract: Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Guo
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Cheng-Dong
authors.initials: CD
authors.lastname: Ji
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Xiang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Third Military Medical University, Chongqing, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D000080027:Cyclams; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D001596:Benzylamines; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D050659:Core Binding Factor Alpha 1 Subunit; D000080027:Cyclams; D006571:Heterocyclic Compounds; C493709:RUNX2 protein, human; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: CXCR4; RUNX2; gastric cancer; invasion; metastasis