title: The role of EGF-EGFR signalling pathway in hepatocellular carcinoma inflammatory microenvironment.
abstract: Epidermal growth factor (EGF) and their receptor (EGFR) play an important role in the development of cancer proliferation, and metastasis, although the mechanism remains unclear. The present study aimed at investigating the role of EGF-EGFR signalling pathway in the development of human hepatocellular carcinoma (HCC) inflammatory environment. Gene profiles of inflammatory cytokines from HCC were measured. Cell bio-behaviours of HCC with low or high metastasis were detected by the live cell monitoring system. Cell proliferation was measured by CCK8. The protein level of CXCL5 and CXCL8 was measured by ELISA. The phosphorylation of PI3K, ERK, MAPK was measured by western blot. EGF significantly induced cell proliferation in HepG2 cells, but not in HCCLM3 cells. EGF prompted the cell movement in both HepG2 and HCCLM3 and regulated the production of CXCL5 and CXCL8 from HCC, which were inhibited by EGFR inhibitor, Erk inhibitor (U0126), or PI3K inhibitors (BEZ-235 and SHBM1009). HCC proliferation, metastasis and production of inflammatory cytokines were regulated via EGF-EGFR signal pathways. CXCL5 could interact with CXCL8, possibly by CXCR2 or the cross-talk between CXCR2 and EGFR. EGF-EGFR signaling pathway can be the potential target of therapies for HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Peixin
authors.initials: P
authors.lastname: Huang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Bijun
authors.initials: B
authors.lastname: Zhu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Jingling
authors.initials: J
authors.lastname: Xia
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011804:Quinolines / Q000494:pharmacology; D020239:Receptor Cross-Talk; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D059016:Tumor Microenvironment
chemical_list: D002070:Butadienes; D054365:Chemokine CXCL5; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D007093:Imidazoles; D016209:Interleukin-8; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; D023063:Receptors, Interleukin-8B; C486263:CXCL5 protein, human; C508606:CXCL8 protein, human; C113580:U 0126; C512478:EGFR protein, human; C531198:dactolisib
keywords: CXCL5; CXCL8; EGF; EGFR; hepatocellular carcinoma; migration; proliferation