By Daniel Walocha ‘19

Angiogenesis is the formation of blood vessels. Cancer cells release growth factors associated with the induction of angiogenesis. Newly formed blood vessels allow cancer cells to easily metastasize, making treatment and survivability difficult for tumors. Colorectal cells are the third leading cause of cancer deaths, so understanding potential therapeutic targets is of interest to researchers.

Shaoxin Cai, Ph.D, from Tongji Hospital analyzed Drosophila Eyes Absent Homologue 1 (EYA1), an important gene overexpressed in colorectal cancer cells. The gene product associates with hypoxia-inducible factor 1 (HIF-1a) to increase the expression of vascular endothelial growth factor (VEGF-A), which directly induces angiogenesis. The pathway was studied in vitro using LoVo, SW620, and other cancer cell lines. The cells were tested for blood vessel formation via a tube formation assay. The EYA1 gene was transfected into the cells using a pLenti assay, and the pathway targets of VEGF-A and HIF-1a were analyzed with an ELISA assay. It was found that EYA1 mediates HIF-1a expression by activating the phosphatidylinositol 3-kinase (PI3K) signaling pathway commonly modified in other cancers. Reverse PCR and western blots confirmed the upregulation of HIF-1a and VEGF-A. EYA1 was therefore found to be an important contributor in regulating cancer cell angiogenesis.

Future studies should focus on developing drug targets for EYA1 inhibition, and testing the gene’s affect in vivo studies.

References:

1. S. Cai, et al. EYA1 promotes tumor angiogenesis by activating the PI3K pathway in colorectal cancer. Experimental Cell Research (2018). doi: 10.1016/j.yexcr.2018.02.028.
2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Blood_vessels-3D_rendering.jpg