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bioRxiv · 10.1101/2020.03.20.000463

SGK1 Signaling Promotes Glucose Metabolism and Survival in Extracellular Matrix Detached Cells

Mason, J. A.·Cockfield, J. A.·Pape, D. J.·Meissner, H.·Sokolowski, M.·White, T. C.·Valentin Lopez, J. C.·Liu, J.·Liu, X.·Martinez-Reyes, I.·Chandel, N. S.·Locasale, J. W.·Schafer, Z. T.
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Abstract

Loss of integrin-mediated attachment to extracellular matrix (ECM) proteins can trigger a variety of cellular changes that impact cell viability. Foremost among these is the activation of anoikis, caspase-mediated cell death induced by ECM-detachment. In addition to anoikis, loss of ECM-attachment causes profound alterations in cellular metabolism that 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 due to 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 unmask SGK1 as master regulator of glucose metabolism and cell survival during ECM-detached conditions.

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Mason, J. A., Cockfield, J. A., Pape, D. J., Meissner, H., Sokolowski, M., White, T. C., Valentin Lopez, J. C., Liu, J., Liu, X., Martinez-Reyes, I., Chandel, N. S., Locasale, J. W., Schafer, Z. T.. 2020-03-20. SGK1 Signaling Promotes Glucose Metabolism and Survival in Extracellular Matrix Detached Cells. https://doi.org/10.1101/2020.03.20.000463

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