Despite advances in treatment regimens, one-third of colorectal cancer (CRC) patients will die from this metastatic disease that can disseminate, or spread, throughout the body. Therefore, understanding the mechanisms underlying the multistep metastatic program of CRC cells is critical for the development of novel therapies that will improve the management of this advanced disease. Our preliminary data indicate that a ubiquitin-like protein, UBXN2A, function as mTORC2 inhibitor in colon cancer cell lines. Our flow cytometry and western blot experiments revealed that induction of UBXN2A with Doxycycline or enhancement of UBXN2A expression with a pharmacological tool, Veratridine, inhibits mTORC2 complex in primary and metastatic colon cancer cells. Based on these results, we hypothesized that increased expression of UBXN2A suppresses the vascular endothelial growth factor, or VEGF protein, which is a key factor in tumor angiogenesis. Our current results indicate that the induction of UBXN2A significantly reduces VEGF protein, a key component in tumor invasion and metastasis. Collectively, our results suggest UBXN2A is a potential key player in intercepting the angiogenesis pathway and downstream regulators of metastasis by suppressing VEGF protein. These findings provide an attractive and promising target for the treatment of metastatic CRC.

Citation Format: Morgan Eikanger, Rekha Srinivasan, Sanam Sane, Khosrow Rezvani. UBXN2A inhibits tumor invasion and metastasis by targeting the mTORC2-VEGF pathway [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3934.