Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?
Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?
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DOI：
10.1017/s002966511500004x
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发表时间：
2015-08-01
影响因子：
7
通讯作者：
Mathers, John C.
中科院分区：
文献类型：
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作者：
Malcomson, Fiona C.;Willis, Naomi D.;Mathers, John C.
流行病学和实验证据表明，包括抗性淀粉在内的不可消化碳水化合物 (NDC) 可以预防结直肠癌。这些抗肿瘤作用被认为是由结肠发酵产生 SCFA（丁酸盐）所致，SCFA 与 G 蛋白偶联受体 GPR43 结合，调节炎症和其他癌症相关过程。 WNT 通路通过调节细胞增殖和迁移等过程，对于维持大肠内的稳态至关重要，并且在结直肠癌中经常异常过度激活。异常的 WNT 信号传导可导致隐窝细胞不规则增殖，从而有利于过度增殖状态。丁酸盐已被证明可以积极调节 WNT 通路，影响细胞凋亡和增殖等功能结果。丁酸盐调节基因表达的能力源于表观遗传机制，包括其作为组蛋白脱乙酰酶抑制剂的作用以及通过调节 DNA 甲基化和 microRNA 的表达。我们得出的结论是，WNT 信号通路的遗传和表观遗传调节可能是抗性淀粉发酵丁酸和其他 NDC 发挥化学保护作用的重要机制。
Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown tomodulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.