來自試管研究和動(dòng)物研究的實(shí)驗(yàn)證據(jù)表明,，抗氧化劑也許能抑制癌癥形成,，盡管有關(guān)其在臨床條件下的效果還幾乎沒有結(jié)論性證據(jù),。然而，發(fā)現(xiàn)在某些條件下抗氧化劑能幫助促進(jìn)癌細(xì)胞存活和增殖卻有點(diǎn)兒出乎意料,。
正常表皮細(xì)胞如果與在結(jié)構(gòu)上具有支持作用的細(xì)胞外基質(zhì)脫離時(shí)就會(huì)死亡,，但在乳腺癌中，引起癌癥的基因如erbB2能為脫離的腫瘤發(fā)生細(xì)胞提供存活信號(hào),。
Schafer等人發(fā)現(xiàn),，細(xì)胞脫離還會(huì)引起代謝缺陷，這些缺陷被erbB2和被抗氧化劑都可挽救,，抗氧化劑似乎是通過經(jīng)由脂肪酸氧化提升細(xì)胞能量水平來發(fā)揮作用的,。這些發(fā)現(xiàn)指出了一些新的機(jī)制，它們有可能被癌細(xì)胞利用,，來增強(qiáng)自己在被改變的基質(zhì)環(huán)境中的存活能力,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 461, 109-113 (3 September 2009) | doi:10.1038/nature08268
Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment
Zachary T. Schafer1,4, Alexandra R. Grassian1,5, Loling Song1,5, Zhenyang Jiang1, Zachary Gerhart-Hines2,3, Hanna Y. Irie1, Sizhen Gao1, Pere Puigserver1,2 & Joan S. Brugge1
1 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
2 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
3 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
4 Present address: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA.
5 These authors contributed equally to this work.
Normal epithelial cells require matrix attachment for survival, and the ability of tumour cells to survive outside their natural extracellular matrix (ECM) niches is dependent on acquisition of anchorage independence1. Although apoptosis is the most rapid mechanism for eliminating cells lacking appropriate ECM attachment2, recent reports suggest that non-apoptotic death processes prevent survival when apoptosis is inhibited in matrix-deprived cells3, 4. Here we demonstrate that detachment of mammary epithelial cells from ECM causes an ATP deficiency owing to the loss of glucose transport. Overexpression of ERBB2 rescues the ATP deficiency by restoring glucose uptake through stabilization of EGFR and phosphatidylinositol-3-OH kinase (PI(3)K) activation, and this rescue is dependent on glucose-stimulated flux through the antioxidant-generating pentose phosphate pathway. Notably, we found that the ATP deficiency could be rescued by antioxidant treatment without rescue of glucose uptake. This rescue was found to be dependent on stimulation of fatty acid oxidation, which is inhibited by detachment-induced reactive oxygen species (ROS). The significance of these findings was supported by evidence of an increase in ROS in matrix-deprived cells in the luminal space of mammary acini, and the discovery that antioxidants facilitate the survival of these cells and enhance anchorage-independent colony formation. These results show both the importance of matrix attachment in regulating metabolic activity and an unanticipated mechanism for cell survival in altered matrix environments by antioxidant restoration of ATP generation.
