Author ORCID Identifier
0009-0005-4595-5972
Date of Award
Spring 4-29-2026
Document Type
Honors Thesis
Department/Major
Basic Biomedical Science
First Advisor
Dr. Khosrow Rezvani
Second Advisor
Dr. Prathapan Ayyappan
Third Advisor
Morgan Eikanger
Keywords
Colon Cancer, Patient-Derived Xenograft (PDX) Cells, UBXN2A, Rictor, mTORC2, pAKT-473, Veratridine (VTD)
Subject Categories
Cellular and Molecular Physiology | Oncology
Abstract
Colorectal cancer (CRC) remains the second deadliest and fourth most common cancer in the world. The metastatic form of CRC is especially devastating due to a lack of effective and safer therapeutic options. Another challenge includes an increasing number of younger patients. Among critical signaling pathways overactivated in CRC, mTORC2 plays a key role in the progression of metastatic CRC, yet there is no selective mTORC2 inhibitor in the clinic. Interestingly, a natural plant alkaloid from the Veratrum genus, Veratridine (VTD), shows promise as VTD can upregulate UBXN2A, a colon-specific tumor suppressor protein. UBXN2A works with E3 ligases to ubiquitinate a specific set of substrates, including the protein Rictor, the key player in the mTORC2 complex. UBXN2A enhances ubiquitination and proteasomal degradation of Rictor, thereby reducing AKT phosphorylation at Serine473, a downstream target of mTORC2 complex. With reduced pAKT473, the cancer cell environment can shift away from proliferation, migration, invasion, and angiogenesis toward elevated cell death via apoptosis. Using Patient-Derived Xenograft (PDX) cells as our model, we were able to replicate the genetic and morphological identity of human tumors, allowing us to characterize the effects of VTD on these cells using a set of Western blots employing an automated, capillary-based Western blot called JESS. This technology enabled us to measure VTD levels in PDX cell lines quantitatively. Together, the results support the anti-mTORC2 function of VTD in human cancer cells.
Recommended Citation
Montgomery, Morgan Daniel, "Veratridine Suppresses Rictor-mTORC2 Signaling Pathway in Colon Cancer Patient-Derived Xenograft Cells" (2026). Honors Thesis. 426.
https://red.library.usd.edu/honors-thesis/426