title: EGFRvIII mediates hepatocellular carcinoma cell invasion by promoting S100 calcium binding protein A11 expression.
abstract: Epidermal growth factor receptor (EGFR) is frequently aberrantly expressed in cancer, and abnormal signalling downstream of this receptor contributes to tumour growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. Aberrant signalling downstream of this receptor contributes to tumour invasion. We previously reported that EGFRvIII can promote hepatocellular carcinoma (HCC) invasion. However, little is known concerning the mechanisms underlying EGFRvIII-mediated increases in cell motility and invasion in HCC. In this study, we observed that S100A11 was significantly upregulated in Huh-7 cells that overexpressed EGFRvIII. Moreover, S100A11 expression was elevated in HCC tissue samples (68.6%; 35/51), and this elevation was correlated with EGFRvIII expression (p = 0.0020; n = 20). Furthermore, the overexpression of S100A11 can promote HCC cell invasiveness, whereas siRNA against S100A11 can suppress the invasiveness of HCC cells stably transfected with EGFRvIII. Additionally, STAT3 inhibitors can block S100A11 expression and S100A11 promoter activity in HCC cells with stable overexpression of EGFRvIII. Furthermore, mutation in STATx binding sites could abolish the S1000A11 promoter activity stimulation by EGFRvIII. Taken together, the results demonstrate that the EGFRvIII-STAT3 pathway promotes cell migration and invasion by upregulating S100A11.
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Research Institute, University of South China; Hengyang, Hunan, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Cancer Research Institute, University of South China; Hengyang, Hunan, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Long
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Bizhi
authors.initials: B
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; D009418:S100 Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C410723:epidermal growth factor receptor VIII; C072337:S100A11 protein, human; D066246:ErbB Receptors