Tumour-suppressive function of SIRT4 in human colorectal cancer.
Tumour-suppressive function of SIRT4 in human colorectal cancer.
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DOI：
10.1038/bjc.2015.226
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发表时间：
2015-07-28
影响因子：
8.8
通讯作者：
Ishii H
中科院分区：
文献类型：
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作者：
Miyo M;Yamamoto H;Konno M;Colvin H;Nishida N;Koseki J;Kawamoto K;Ogawa H;Hamabe A;Uemura M;Nishimura J;Hata T;Takemasa I;Mizushima T;Doki Y;Mori M;Ishii H
SIRT4定位于线粒体，是烟酰胺腺嘌呤二核苷酸依赖酶sirtuin家族中最不具特征的成员之一，在代谢、应激反应和寿命等多种细胞过程中发挥关键作用。只有少数研究描述了它的功能，并评估了它在人类癌症中的临床意义。我们建立了过表达SIRT4的结直肠癌细胞系（SW480、HCT116和HT29），并研究了它们对增殖、迁移和侵袭的影响，以及负调控肿瘤侵袭和转移的E-cadherin的表达。通过免疫组织化学评估结直肠癌标本中SIRT4表达与临床病理特征及预后的关系。SIRT4通过抑制谷氨酰胺代谢，上调E-cadherin表达，抑制结直肠癌细胞的增殖、迁移和侵袭。此外，SIRT4在结直肠癌中的表达随着侵袭和转移的进展而降低，SIRT4的低表达与预后较差相关。SIRT4具有肿瘤抑制功能，可能成为结直肠癌新的治疗靶点。
SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers. We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry. SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis. SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.