Anticancer activity of the cholesterol exporter ABCA1 gene.
Anticancer activity of the cholesterol exporter ABCA1 gene.
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胆固醇出口商ABCA1基因的抗癌活性。
DOI：
10.1016/j.celrep.2012.08.011
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发表时间：
2012-09-27
期刊：
影响因子：
8.8
通讯作者：
Land H
中科院分区：
文献类型：
--
作者：
Smith B;Land H
ABCA1蛋白介导细胞胆固醇跨质膜转移向载脂蛋白A-I。 ABCA1基因的功能丧失突变诱导丹吉疾病和家族性降低脂肪蛋白血症，这都是心血管疾病，其特征是血清胆固醇异常低，巨噬细胞中胆固醇的升高以及随后形成血管斑块。在癌细胞中也经常发现细胞内胆固醇水平的增加。在这里，我们证明了ABCA1外排功能的抗癌活性，在通过致癌突变或癌症特异性ABCA1功能丧失突变抑制ABCA1基因表达后，这会损害。与在癌细胞中发现的胆固醇合成升高时，ABCA1缺乏症可以增加线粒体胆固醇，抑制线粒体细胞死亡促进分子的释放，从而促进癌细胞的存活，从而促进了升高的线粒体胆固醇对癌症的胆固醇至关重要。
The ABCA1 protein mediates the transfer of cellular cholesterol across the plasma membrane to apolipoprotein A-I. Loss-of-function mutations in the ABCA1 gene induce Tangier disease and familial hypoalphalipoproteinemia, both cardio-vascular conditions characterized by abnormally low levels of serum cholesterol, increased cholesterol in macrophages and subsequent formation of vascular plaque. Increased intra-cellular cholesterol levels are also frequently found in cancer cells. Here we demonstrate anti-cancer activity of ABCA1 efflux function, which is compromised following inhibition of ABCA1 gene expression by oncogenic mutations or cancer-specific ABCA1 loss-of-function mutations. In concert with elevated cholesterol synthesis found in cancer cells, ABCA1 deficiency allows for increased mitochondrial cholesterol, inhibits release of mitochondrial cell death-promoting molecules and thus facilitates cancer cell survival, overall suggesting that elevated mitochondrial cholesterol is essential to the cancer phenotype.
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影响因子：
4.7
作者：
Graziani, SR;Igreja, FAF;Maranhao, RC
通讯作者：
Maranhao, RC
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8.8
作者：
Dessi, S;Batetta, B;Anchisi, C;Pani, P;Costelli, P;Tessitore, L;Baccino, F M
通讯作者：
Baccino, F M
影响因子：
10.3
作者：
Benn, Marianne;Tybjaerg-Hansen, Anne;Nordestgaard, Borge G.
通讯作者：
Nordestgaard, Borge G.
影响因子：
4.8
作者：
Brusselmans, Koen;Timmermans, Leen;Swinnen, Johannes V.
通讯作者：
Swinnen, Johannes V.