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Paper Reading Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness  Shuhua Yue,1 Junjie Li,2 Seung-Young Lee,1 Hyeon Jeong Lee,3 Tian Shao,4 Bing Song,2 Liang Cheng,5Timothy A. Masterson,6 Xiaoqi Liu,4,7 Timothy L. Ratliff,3,7 and Ji-Xin Cheng1,7,* Cell Metabolism Some previous research reports indicate that altered lipid metabolism is increasingly recognized as a signature of cancer cells. In this paper, firstly, through integrated analyses of prostate cancer clinical samples, cell lines, and mouse xenograft model by Raman Spectromicroscopy, the authors have revealed that accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Because expression levels of AR are heterogeneous and even absent in some metastases. Such clinical observations suggest that PCa cells may also depend on other compensatory signaling pathways to survive and grow. One of the most important pathways that bypasses AR is the PI3K/AKT/mTOR pathway, which is negatively regulated by the tumor suppressor PTEN. Then, they proved that CE accumulation in PCa is not correlated with androgen signaling, they further showed CE accumulation is induced by PTEN Loss and PI3K/AKT Activation , and they found CE accumulation in PCa Cells arises from enhanced uptake of exogenous LDL. next, CE depletion reduces PCa Cells proliferation by limiting the uptake of essential fatty acids.This finding elucidates the mechanism by which PTEN regulates metabolic pathways to meet the increased demand of aggressive PCa cell for LDL cholesterol uptake. This paper offers a biological foundation that supports the beneficial effect of cholesterol-lowering drugs. http://dx./10.1016/j.cmet.2014.01.019 SREBP Activity Is Regulated by mTORC1 and Contributes to Akt-Dependent Cell Growth  Thomas Porstmann,1 Claudio R. Santos,1,7 Beatrice Griffiths,1,7 Megan Cully,2 Mary Wu,3Sally Leevers,4 John R. Griffiths,5 Yuen-Li Chung,6 and Almut Schulze1,* Cell Metabolism In this paper, the authors observed significant accumulation of fatty acids and phosphoglycerides in response to Akt activation and enhanced incorporation of labeled glucose, pyruvate, or acetate into the lipid fraction in cells with activated Akt, all of which was blocked by rapamycin. These results show that Akt activates de novo lipogenesis and that mTORC1 activity is required for this effect. Firstly ,they used 1% lipoprotein deficient serum (LPDS) to reduce activation of endogenous Akt and limit the availability of exogenous lipids, found that activation of myrAkt-ER by addition of 4-hydroxytamoxifen (4-OHT) caused a 20%–30% increase in median cell volume. They next used nuclear magnetic resonance spectroscopy to measure changes in medium metabolite concentration before and after myrAkt-ER activation. They observed a reduction in Akt-dependent amino acid uptake and cellular amino acid content by rapamycin treatment. Because studies in knockout mice have shown selective involvement of SREBP1a and 1c in the regulation of lipid biosynthesis. then, they proved that Akt induces rapid accumulation of mSREBP1 in the nucleus. furthermore, they found that Akt-dependent activation of SREBP1 and lipogenesis requires mTORC1 activity .at same time, they found silencing of SREBP1 restricts Akt-induced cell growth in mammalian cells and reduced cell and organ size in drosophila, This result confirms that SREBP-dependent gene expression represents an important mechanism in the regulation of lipogenesis during cell growth. 10.1016/j.cmet.2008.07.007 Edited by Biaolong Deng  点击文首蓝字，关注我们 每一段文字都想与你分享 |
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