title: Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumour metastasis in head and neck squamous cell carcinoma.
abstract: Epidermal growth factor (EGF) is important for cancer cell proliferation, angiogenesis and metastasis in many types of cancer. However, the mechanisms involved in EGF-induced head and neck squamous cell carcinoma (HNSCC) metastasis remain largely unknown. In this study, we reveal that angiopoietin-like 4 (ANGPTL4) plays an important role in the regulation of EGF-induced cancer metastasis. We showed that EGF-induced ANGPTL4 expression promoted anoikis resistance and cancer cell migration and invasion in HNSCC. In addition, depletion of ANGPTL4 inhibited EGF-induced cancer cell invasion. Autocrine production of EGF-induced ANGPTL4 regulated the expression of matrix metalloproteinases (MMPs). The induction of MMP-1 gene expression by ANGPTL4-activated integrin β1 signalling occurred through the AP-1 binding site in the MMP-1 gene promoter. Furthermore, down-regulation of MMP-1 impeded EGF- and recombinant ANGPTL4-enhanced HNSCC cell migration and invasion. Depletion of ANGPTL4 significantly blocked EGF-primed extravasation and metastatic seeding of tumour cells and MMP-1 expression in lungs. However, no effect of ANGPTL4 on tumour growth was observed. These results suggest that EGF-induced expression and autocrine production of ANGPTL4 enhances HNSCC metastasis via the up-regulation of MMP-1 expression. Inhibition of ANGPTL4 expression may be a potential strategy for the treatment of EGFR-mediated HNSCC metastasis.
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Y-H
authors: YH
authors: Liao
authors: Department of Chest Medicine, Chi Mei Medical Center, Tainan, Taiwan, ROC.
authors: K-H
authors: KH
authors: Chiang
authors: Department of Chest Medicine, Chi Mei Medical Center, Tainan, Taiwan, ROC.
authors: J-M
authors: JM
authors: Shieh
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
authors: C-R
authors: CR
authors: Huang
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: C-J
authors: CJ
authors: Shen
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.|Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, ROC.
authors: W-C
authors: WC
authors: Huang
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.|Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.|Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC.
authors: B-K
authors: BK
authors: Chen
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D023102:Anoikis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000502:physiology*; D016758:Genes, jun; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D019012:Integrin beta1; D004815:Epidermal Growth Factor; D020781:Matrix Metalloproteinase 1