Tumor mechanics and metabolic dysfunction

Jason C. Tung, J. Matthew Barnes, Shraddha R. Desai, Christopher Sistrunk, Matthew W. Conklin, Pepper Schedin, Kevin W. Eliceiri, Patricia J. Keely, Victoria L. Seewaldt, Valerie M. Weaver

Research output: Contribution to journalReview article

62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)269-280
Number of pages12
JournalFree Radical Biology and Medicine
Volume79
DOIs
StatePublished - Feb 2015

Keywords

  • Cancer
  • ECM stiffness
  • Free radicals
  • Mechanosignaling
  • Tumor metabolism
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Tung, J. C., Barnes, J. M., Desai, S. R., Sistrunk, C., Conklin, M. W., Schedin, P., Eliceiri, K. W., Keely, P. J., Seewaldt, V. L., & Weaver, V. M. (2015). Tumor mechanics and metabolic dysfunction. Free Radical Biology and Medicine, 79, 269-280. https://doi.org/10.1016/j.freeradbiomed.2014.11.020