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

Article

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. Keywords:

Attributes

Attribute NameValues
Creator
  • Jason Mason

  • Jordan A. Cockfield

  • Daniel Pape

  • Hannah Meissner

  • Michael Sokolowski

  • Taylor C. White

  • Jose Valentin Lopez

  • Juan Liu

  • Xiaojing Liu

  • Inmaculada martinez-Reyes

  • Navdeep Chandel

  • Jason Locasale

  • Zachary Schafer

Journal or Work Title
  • bioRivx

Publication Date
  • 2020-03

Subject
  • Deltavision Deconvolution Microscope

Publisher
  • Cold Spring Harbor

Date Created
  • 2020-07-09

Language
  • English

Departments and Units
Record Visibility Public
Content License
  • All rights reserved

Digital Object Identifier

doi:10.1101/2020.03.20.000463

This DOI is the best way to cite this article.