SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Mason, JA; Cockfield, JA; Pape, DJ; Meissner, H; Sokolowski, MT; White, TC; Valentín López, JC; Liu, J; Liu, X; Martínez-Reyes, I; Chandel, NS; Locasale, JW; Schafer, ZT

Published Date

  • March 16, 2021

Published In

Volume / Issue

  • 34 / 11

Start / End Page

  • 108821 -

PubMed ID

  • 33730592

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.108821

Language

  • eng

Conference Location

  • United States