Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis.

Published

Journal Article

Successful metastasis requires the co-evolution of stromal and cancer cells. We used stable isotope labeling of amino acids in cell culture coupled with quantitative, label-free phosphoproteomics to study the bidirectional signaling in ovarian cancer cells and human-derived, cancer-associated fibroblasts (CAFs) after co-culture. In cancer cells, the interaction with CAFs supported glycogenolysis under normoxic conditions and induced phosphorylation and activation of phosphoglucomutase 1, an enzyme involved in glycogen metabolism. Glycogen was funneled into glycolysis, leading to increased proliferation, invasion, and metastasis of cancer cells co-cultured with human CAFs. Glycogen mobilization in cancer cells was dependent on p38α MAPK activation in CAFs. In vivo, deletion of p38α in CAFs and glycogen phosphorylase inhibition in cancer cells reduced metastasis, suggesting that glycogen is an energy source used by cancer cells to facilitate metastatic tumor growth.

Full Text

Duke Authors

Cited Authors

  • Curtis, M; Kenny, HA; Ashcroft, B; Mukherjee, A; Johnson, A; Zhang, Y; Helou, Y; Batlle, R; Liu, X; Gutierrez, N; Gao, X; Yamada, SD; Lastra, R; Montag, A; Ahsan, N; Locasale, JW; Salomon, AR; Nebreda, AR; Lengyel, E

Published Date

  • January 8, 2019

Published In

Volume / Issue

  • 29 / 1

Start / End Page

  • 141 - 155.e9

PubMed ID

  • 30174305

Pubmed Central ID

  • 30174305

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2018.08.007

Language

  • eng

Conference Location

  • United States