title: Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms.
abstract: Caveolins are a family of membrane-bound scaffolding proteins that compartmentalize and negatively regulate signal transduction. Recent studies have implicated a loss of caveolin-1 (Cav-1) expression in the pathogenesis of human cancers. Loss of Cav-1 expression in cancer-associated fibroblasts results in an activated tumor microenvironment, thereby driving early tumor recurrence, metastasis, and poor clinical outcome in breast and prostate cancers. We describe various paracrine signaling mechanism(s) by which the loss of stromal Cav-1 promotes tumor progression, including fibrosis, extracellular matrix remodeling, and the metabolic/catabolic reprogramming of cancer-associated fibroblast, to fuel the growth of adjacent tumor cells. It appears that oxidative stress is the root cause of initiation of the loss of stromal Cav-1 via autophagy, which provides further impetus for the use of antioxidants in anticancer therapy. Finally, we discuss the functional role of Cav-1 in epithelial cancer cells.
authors.affiliation: The Jefferson Stem Cell Biology and Regenerative Medicine Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. federica.sotgia@jefferson.edu
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.forename: Ubaldo E
authors.initials: UE
authors.lastname: Martinez-Outschoorn
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: Stephanos
authors.initials: S
authors.lastname: Pavlides
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000818:Animals; D001343:Autophagy; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018384:Oxidative Stress; D019899:Paracrine Communication; D059016:Tumor Microenvironment
chemical_list: D051242:Caveolin 1