title: SEMA3F prevents metastasis of colorectal cancer by PI3K-AKT-dependent down-regulation of the ASCL2-CXCR4 axis.
abstract: Semaphorin-3F (SEMA3F), an axonal repulsant in nerve development, has been shown to inhibit the progression of human colorectal cancer (CRC); however, the underlying mechanism remains elusive. In this study we found a negative correlation between the levels of SEMA3F and CXCR4 in CRC specimens from 85 patients, confirmed by bioinformatics analysis of gene expression in 229 CRC samples from the Cancer Genome Atlas. SEMA3F(high) /CXCR4(low) patients showed the lowest frequency of lymph node and distant metastasis and the longest survival. Mechanistically, SEMA3F inhibited the invasion and metastasis of CRC cells through PI3K-AKT-dependent down-regulation of the ASCL2-CXCR4 axis. Specifically, ASCL2 enhanced the invasion and metastasis of CRC cells in vitro and expression of ASCL2 correlated with distant metastasis, tumour size and poor overall survival in CRC patients. Treatment of CRC cells with the CXCR4 antagonist AMD3100 attenuated SEMA3F knockdown-induced invasion and metastasis of CRC cells in vitro and in vivo. Our study thus demonstrates that SEMA3F functions as a suppressor of CRC metastasis via down-regulating the ASCL2-CXCR4 axis.
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Zhi-hang
authors: ZH
authors: Zhou
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Jun
authors: J
authors: Rao
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Jing
authors: J
authors: Yang
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Feng
authors: F
authors: Wu
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Juan
authors: J
authors: Tan
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Sen-lin
authors: SL
authors: Xu
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors: Yanqing
authors: Y
authors: Ding
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors: Na
authors: N
authors: Zhan
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Xu-gang
authors: XG
authors: Hu
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: You-hong
authors: YH
authors: Cui
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Xia
authors: X
authors: Zhang
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors: Weiguo
authors: W
authors: Dong
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Xin-dong
authors: XD
authors: Liu
authors: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Key Laboratory of Tumour Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.
authors: Xiu-wu
authors: XW
authors: Bian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D045325:HCT116 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D058539:Phosphatidylinositol 3-Kinase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019718:Receptors, CXCR4; C065501:ASCL2 protein, human; C527276:CXCR4 protein, human; C491230:SEMA3F protein, human
keywords: ASCL2; CXCR4; SEMA3F; colorectal cancer; metastasis