EYA1 promotes tumor angiogenesis by activating the PI3K pathway in colorectal cancer

• Published in: Experimental cell research 2018-06, Vol.367 (1), p.37-46
• Main Authors: Cai, Shaoxin, Cheng, Xuefei, Liu, Yi, Lin, Zhizun, Zeng, Wei, Yang, Changshun, Liu, Lihang, Chukwuebuka, Ozor Anthony, Li, Weihua
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANGIOGENESIS; Animals; BLOOD VESSELS; Caco-2 Cells; Colorectal cancer; Colorectal Neoplasms - blood supply; DROSOPHILA; EYA1; Female; GROWTH FACTORS; HT29 Cells; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; NEOPLASMS; Neovascularization, Pathologic - genetics; Nuclear Proteins - genetics; Phosphatidylinositol 3-Kinase - metabolism; PI3K pathway; Protein Tyrosine Phosphatases - genetics; TUMOR CELLS; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Xenograft Model Antitumor Assays
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2018.02.028

Blood vessels are one of the major routes for the dissemination of cancer cells. Malignant tumors release growth factors such as vascular endothelial growth factor(VEGF) to induce angiogenesis, thereby promoting metastasis. Here, we report that The Drosophila Eyes Absent Homologue 1 (EYA1), which is overexpressed in colorectal tumor cells, can promote colorectal tumor angiogenesis by coordinating with the hypoxia-inducible factor 1 (HIF-1α) to increase the expression of VEGF-A. Moreover, data indicated that the enhancement of HIF-1α expression by Eya1 depended on its ability to activate the phosphatidylinositol 3-kinase (PI3K) signaling pathways to increase the phosphorylation of AKT subunits. Overexpression of Eya1 increased tumor angiogenesis in vivo and in vitro. Our study suggested that Eya1 is essential in regulating cancer cell-mediated angiogenesis and contributes to tumor growth, and that Eya1 provides a potential and specific target for new anti-angiogenesis drug development. •EYA1 promotes colorectal tumor angiogenesis.•EYA1 co-ordinates with HIF-1α to increase VEGF-A expression.•This depended on activation of PI3K signaling by EYA1.•EYA1 is a target for anti-angiogenesis drug development in cancer.