Schroll Monica M, Ludwig Katelyn R, Bauer Kerry M, Hummon Amanda B
Department of Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Metabolites. 2018 Jan 11;8(1):5. doi: 10.3390/metabo8010005.
Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side) colon is different from cancer of the descending (left side) colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.
维生素D缺乏是一个全球性的常见问题。特别是在北半球，紫外线B辐射不易穿透大气层，这一问题更为突出。维生素D缺乏与结直肠癌的发病率和死亡率之间存在关联。此外，有强有力的证据表明，升结肠（右侧）癌与降结肠（左侧）癌在预后、肿瘤分化、息肉类型以及分子水平方面存在差异。右侧肿瘤的Wnt信号通路增强，更容易复发，而左侧肿瘤的抑癌基因表达降低。本研究旨在了解维生素D的活性代谢产物骨化三醇治疗右侧和左侧结肠癌所导致的蛋白质组和代谢组变化。我们的结果表明，与右侧结肠癌相比，用骨化三醇治疗的左侧结肠癌在蛋白质组和代谢组方面的变化数量要多得多。我们发现，骨化三醇治疗右侧和左侧结肠癌均会导致核糖体蛋白L37和蛋白S100A10的下调。这两种蛋白质都与肿瘤发生密切相关，提示了维生素D水平低与结肠癌之间相关性的一种可能机制。
