Article Impact Level: HIGH Data Quality: STRONG Summary of American Journal of Lifestyle Medicine, 15598276251339396. https://doi.org/10.1177/15598276251339396 Dr. Vanita Rahman et al.
Points
- This study found that loss of SOX9 accelerates colorectal cancer progression by promoting epithelial-mesenchymal transition and metastasis through increased SOX2 expression in mouse models.
- Human colorectal cancer samples showed that about 20 percent lacked SOX9 protein, a condition linked to higher tumor grade and poorer patient outcomes.
- A separate analysis of 376 patients confirmed that lower SOX9 gene expression correlated with earlier diagnosis, greater lymph node involvement, and reduced survival.
- Promoter methylation was identified as a likely mechanism for SOX9 silencing, reinforcing its role as a tumor suppressor in colorectal cancer.
- These findings suggest that therapies targeting SOX9-related pathways could help manage aggressive colorectal cancer subtypes with poor prognosis.
Summary
This study investigated the role of SOX9 in colorectal cancer (CRC) progression, focusing on its interaction with the Wnt/β-catenin signaling pathway, which is commonly activated due to APC tumor suppressor defects in CRC. In mouse models, the combined inactivation of Apc and Sox9 led to more invasive tumors with epithelial-mesenchymal transition (EMT) and increased SOX2 stem cell factor expression. In an additional model with Apc, Kras, and Trp53 mutations, Sox9 inactivation promoted SOX2 induction and distant metastases, suggesting a critical role for SOX9 in tumor suppression.
In human CRC samples, 20% of tumors exhibited loss of SOX9 protein expression, which correlated with higher tumor grade and poor prognosis. In an independent cohort of 376 CRC patients, low SOX9 gene expression was linked to poorer survival outcomes, earlier age at diagnosis, and increased lymph node involvement. SOX9 expression loss was associated with promoter methylation, further implicating its role as a tumor suppressor in CRC. These findings highlight SOX9’s involvement in CRC progression, where its loss may facilitate tumor invasion and metastasis through the upregulation of EMT and stem cell phenotypes.
The results underscore the tumor-suppressive function of SOX9 in CRC and suggest that its loss could promote CRC progression and metastasis by enhancing EMT characteristics. These insights could inform future therapeutic strategies targeting SOX9 or its regulatory pathways to improve patient outcomes, especially in CRC subtypes with low SOX9 expression associated with worse prognoses.
Link to the article: https://journals.sagepub.com/doi/10.1177/15598276251339396
References Rahman, V., Becker, R., Gray, S., Holubkov, R., Loomis, J., & Barnard, N. (2025). Feasibility and efficacy of a plant-based nutrition intervention for type 2 diabetes in a primary care setting. American Journal of Lifestyle Medicine, 15598276251339396. https://doi.org/10.1177/15598276251339396
