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

Autor: Xiaojing Liu, Jose C. Valentin-Lopez, Jordan A. Cockfield, Daniel J. Pape, Juan Liu, Joshua A. Mason, Inmaculada Martínez-Reyes, Taylor C. White, Hannah Meissner, Navdeep S. Chandel, Jason W. Locasale, Michael Sokolowski, Zachary T. Schafer
Rok vydání: 2021
Předmět:
0301 basic medicine
Programmed cell death
Cell Survival
Glucose uptake
Protein Serine-Threonine Kinases
Carbohydrate metabolism
Pentose phosphate pathway
Glyceraldehyde 3-Phosphate
Oxidative Phosphorylation
General Biochemistry
Genetics and Molecular Biology
Cell Line
Immediate-Early Proteins
Pentose Phosphate Pathway
Extracellular matrix
Mice
03 medical and health sciences
Adenosine Triphosphate
0302 clinical medicine
Cell Adhesion
Animals
Humans
Anoikis
Viability assay
Cell Proliferation
Glucose Transporter Type 1
biology
Chemistry
Extracellular Matrix
Mitochondria
Cell biology
Glucose
030104 developmental biology
biology.protein
GLUT1
Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
Signal transduction
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Cell Reports. 34:108821
ISSN: 2211-1247
Popis: SummaryLoss 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.
Databáze: OpenAIRE
Externí odkaz: