2. Academic Validation
  3. Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis

Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis

  • Cell Metab. 2019 Jan 8;29(1):141-155.e9. doi: 10.1016/j.cmet.2018.08.007.
Marion Curtis 1,  Hilary A Kenny 1,  Bradley Ashcroft 1,  Abir Mukherjee 1,  Alyssa Johnson 1,  Yilin Zhang 1,  Ynes Helou 2,  Raquel Batlle 3,  Xiaojing Liu 4,  Nuria Gutierrez 3,  Xia Gao 4,  S Diane Yamada 1,  Ricardo Lastra 5,  Anthony Montag 5,  Nagib Ahsan 6,  Jason W Locasale 4,  Arthur R Salomon 7,  Angel R Nebreda 8,  Ernst Lengyel 9
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL 60637, USA.
  • 2 Department of Molecular Biology, Cell Biology, and Biochemistry/Center of Genomics and Proteomics, Brown University, Providence, RI 02903, USA.
  • 3 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
  • 4 Department of Pharmacology and Cancer Biology, Duke Cancer Institute, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27705, USA.
  • 5 Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
  • 6 Division of Biology and Medicine, Alpert Medical School, Brown University, Providence, RI 02903, USA; Center for Cancer Research Development, Proteomics Core Facility, Rhode Island Hospital, Providence, RI 02903, USA.
  • 7 Department of Molecular Biology, Cell Biology, and Biochemistry/Center of Genomics and Proteomics, Brown University, Providence, RI 02903, USA; Center for Cancer Research Development, Proteomics Core Facility, Rhode Island Hospital, Providence, RI 02903, USA.
  • 8 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
  • 9 Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL 60637, USA. Electronic address: [email protected].
PMID: 30174305 DOI: 10.1016/j.cmet.2018.08.007
Abstract

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.

Keywords

PGM1; cancer-associated fibroblast; glycogen; glycogen phosphorylase; metabolism; metastasis; omentum; ovarian cancer; p38-MAPK; phosphoproteomics.

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