SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells
SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells
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DOI：
10.1016/j.celrep.2021.108821
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发表时间：
2021-03-16
期刊：
影响因子：
8.8
通讯作者：
Schafer, Zachary T.
中科院分区：
文献类型：
--
作者：
Mason, Joshua A.;Cockfield, Jordan A.;Schafer, Zachary T.
整合素介导的与细胞外基质（ECM）蛋白的附着的丧失可引发影响细胞活力的多种细胞变化。其中最重要的是失巢凋亡的激活，由ECM脱离诱导的半胱天冬酶介导的细胞死亡。此外，ECM附着的丧失导致细胞代谢的深刻改变，这可导致非失巢凋亡依赖性细胞死亡。在这里，我们描述了一个令人惊讶的作用，血清和糖皮质激素激酶-1（SGK 1）在促进能量产生时，细胞分离。我们的数据表明，SGK 1的激活是必要的和足够的ATP生成过程中ECM脱离和锚定独立的增长。更具体地说，由于GLUT 1转录升高，SGK 1促进葡萄糖摄取的显著升高。此外，碳流入戊糖磷酸途径（PPP）是必要的，以适应升高的葡萄糖摄取和PPP介导的甘油醛-3-磷酸（G3 P）是必要的ATP的生产。因此，我们的数据显示SGK 1作为ECM分离条件下葡萄糖代谢和细胞存活的主要调节因子。
Loss of integrin-mediated attachment to extracellular matrix (ECM) proteins can trigger a variety of cellular changes that affect cell viability. Foremost among these is the activation of anoikis, caspase-mediated cell death induced by ECM detachment. In addition, loss of ECM attachment causes profound alterations in cellular metabolism, which can lead to anoikis-independent cell death. Here, we describe a surprising role for serum and glucocorticoid kinase-1 (SGK1) in the promotion of energy production when cells are detached. Our data demonstrate that SGK1 activation is necessary and sufficient for ATP generation during ECM detachment and anchorage-independent growth. More specifically, SGK1 promotes a substantial elevation in glucose uptake because of elevated GLUT1 transcription. In addition, carbon flux into the pentose phosphate pathway (PPP) is necessary to accommodate elevated glucose uptake and PPP-mediated glyceraldehyde-3-phosphate (G3P) is necessary for ATP production. Thus, our data show SGK1 as master regulator of glucose metabolism and cell survival during ECM-detached conditions.