title: Tumor mechanics and metabolic dysfunction.
abstract: Desmosplasia is a characteristic of most solid tumors and leads to fibrosis through abnormal extracellular matrix (ECM) deposition, remodeling, and posttranslational modifications. The resulting stiff tumor stroma not only compromises vascular integrity to induce hypoxia and impede drug delivery, but also promotes aggressiveness by potentiating the activity of key growth, invasion, and survival pathways. Intriguingly, many of the protumorigenic signaling pathways that are mechanically activated by ECM stiffness also promote glucose uptake and aerobic glycolysis, and an altered metabolism is a recognized hallmark of cancer. Indeed, emerging evidence suggests that metabolic alterations and an abnormal ECM may cooperatively drive cancer cell aggression and treatment resistance. Accordingly, improved methods to monitor tissue mechanics and metabolism promise to improve diagnostics and treatments to ameliorate ECM stiffening and elevated mechanosignaling may improve patient outcome. Here we discuss the interplay between ECM mechanics and metabolism in tumor biology and suggest that monitoring these processes and targeting their regulatory pathways may improve diagnostics, therapy, and the prevention of malignant transformation.
authors.affiliation: Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Tung
authors.affiliation: Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Barnes
authors.affiliation: Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Shraddha R
authors.initials: SR
authors.lastname: Desai
authors.affiliation: Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sistrunk
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin Carbone Comprehensive Cancer Center, Wisconsin Institute for Medical Research, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Conklin
authors.affiliation: Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Pepper
authors.initials: P
authors.lastname: Schedin
authors.affiliation: Laboratory for Optical and Computational Instrumentation, Laboratory for Cell and Molecular Biology, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin Carbone Comprehensive Cancer Center, Wisconsin Institute for Medical Research, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Keely
authors.affiliation: Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Seewaldt
authors.affiliation: Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California at San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, CA 94143, USA; Helen Diller Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143, USA. Electronic address: Valerie.Weaver@ucsfmedctr.org.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Weaver
mesh_terms: D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
keywords: Cancer; ECM stiffness; Free radicals; Mechanosignaling; Tumor metabolism; Tumor microenvironment