Abstract 5800: Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumor metastasis in head and neck squamous cell carcinoma

Abstract

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 head and neck squamous cell carcinoma (HNSCC). In addition, depletion of ANGPTL4 inhibited EGF-induced cancer cell invasion. Autocrine production of EGF-induced ANGPTL4 regulated the expression of MMPs. The induction of MMP-1 gene expression by ANGPTL4-activated integrin β1 signaling 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 anoikis resistance and extravasation. Moreover, depletion of ANGPTL4 significantly blocked EGF-primed metastatic seeding of tumor cells and MMP-1 expression in lungs. However, no effect of ANGPTL4 on tumor 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. Citation Format: Yu-Han Liaong. Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumor metastasis in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5800. doi:10.1158/1538-7445.AM2017-5800