Study of TIAM2 overexpression induced tumorigenesis

Abstract

Human T-cell lymphoma invasion and metastasis 2 (a human brain-specific protein) named as TIAM2 short form (TIAM2S) encodes short mRNA isoforms Our previous studies have shown that the TIAM2S in liver cells promotes liver cancer tumorigenesis However the mechanism underlying its oncogenic effect remains unclear This study aims to investigate the role of TIAM2S in spontaneous and carcinogen-induced tumorigenesis We established TIAM2S-overexpressing transgenic (TG) mouse lines and characterized the genotypes and phenotypes in great details In addition we applied an azoxymethane (AOM)-induced colon cancer model to examine tumor susceptibility in these TIAM2S-TG mice We found that the TIAM2S-expressing murine model developed chronic inflammation and had high incidence of lymphocytic infiltration in various organs Furthermore AOM-induced colon tumor developed at a younger age in the TIAM2S-TG mice than in the wild type (WT) mice We examined immune cells and cytokine/chemokine profiles and found that serotonin-mediated inflammatory bowel disease (IBD) particularly IL-23+/IL-17+/CD8+T lymphocytes were characterized in the tertiary lymphoid organs (TLOs) in the TIAM2S-TG mice Overall this study shows that TIAM2S mediates chronic inflammation and increases the susceptibility of colon cells to environmental stresses and leads to the development of colorectal cancer (CRC)

Date of Award	2020
Original language	English
Supervisor	Hsiao-Fang Sun (Supervisor)