title: EGFL7 is an intercellular EGFR signal messenger that plays an oncogenic role in glioma.
abstract: Epidermal Growth Factor like domain 7 (EGFL7), also known as Vascular Endothelial-statin (VE-statin), is a secreted angiogenic factor. Recent data have demonstrated the potential oncogenic role and prognostic significance of EGFL7 in several human cancers. However, the clinical signature and further mechanisms of EGFL7's function in gliomagenesis are poorly understood. In the present study, we found that increased EGFL7 expression was associated with tumor grade. High expression of EGFL7 in EGFRvIII-positive glioblastoma multiforme (GBM) was determined to be a strong and independent risk factor for reduced life expectancy. EGFRvIII cells can secrete the EGFL7 protein to improve the activity of the β-catenin/TCF4 Transcription complex in EGFRwt cells, thus promoting their own EGFL7 expression. Our research demonstrates that oncogenic activation of EGFRwt in GBM is likely maintained by a continuous EGFL7 autocrine flow line, and may be an attractive target for therapeutic intervention.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Fei-Yi-Fan
authors.initials: FY
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Wang-Gou
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Jishou University, Jishou 416000, China.
authors.forename: Chun-Hai
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: lxjneuro@csu.edu.cn.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D019898:Autocrine Communication; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D011485:Protein Binding; D060066:Protein Interaction Maps; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013963:Thyroid Hormones / Q000378:metabolism; D013997:Time Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors; D066246:ErbB Receptors; D008024:Ligands; D008565:Membrane Proteins; D013449:Sulfonamides; D013963:Thyroid Hormones; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; D000097810:Thyroid Hormone-Binding Proteins; C495270:CTNNB1 protein, human; C527877:EGFL7 protein, human; C575430:FH535; C532096:TCF4 protein, human; C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human
keywords: Angiogenesis; EGFL7; EGFRvIII; Glioblastoma; Heterogeneity