High-Mobility Group Box-1 protein (HMGB1) plays a core role in the link between ulcerative colitis (UC) and colorectal cancer (CRC), particularly in colitic carcinoma.
A recent research shows that HMGB1 is significantly overexpressed in UC-related carcinogenesis. This overexpression is associated with key disruptions in mucosal immunity and epithelial differentiation, both of which are crucial in the development of colitic carcinoma.
Specifically, increased HMGB1 levels correspond with decreased activation of CD8+ cells, promoting an immune-tolerant microenvironment. Additionally, HMGB1 facilitates the metabolic reprogramming of CD8+ cells from oxidative phosphorylation to glycolysis, impairing their functionality. This immune modulation contributes to reduced epithelial differentiation, supporting tumor progression in both UC-related and sporadic CRC.
These findings highlight HMGB1 as not only a biomarker for colorectal carcinogenesis but also a potential therapeutic target. Addressing HMGB1-induced immune exhaustion and epithelial dysfunction may open new avenues for treatment in UC-related CRC.
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Read the full article about the study:
https://pubmed.ncbi.nlm.nih.gov/38999957
