Tumor mechanics and metabolic dysfunction.

TitleTumor mechanics and metabolic dysfunction.
Publication TypeJournal Article
Year of Publication2015
AuthorsTung JC, J Barnes M, Desai SR, Sistrunk C, Conklin MW, Schedin P, Eliceiri KW, Keely PJ, Seewaldt VL, Weaver VM
JournalFree Radic Biol Med
Volume79
Pagination269-80
Date Published2015 Feb
ISSN1873-4596
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.

DOI10.1016/j.freeradbiomed.2014.11.020
Alternate JournalFree Radic. Biol. Med.
PubMed ID25532934
PubMed Central IDPMC4339308
Grant ListCA138818-01A1 / CA / NCI NIH HHS / United States
F32 CA174319 / CA / NCI NIH HHS / United States
F32CA174319 / CA / NCI NIH HHS / United States
R01 CA114462 / CA / NCI NIH HHS / United States
R01 CA136590 / CA / NCI NIH HHS / United States
R01 CA136590 / CA / NCI NIH HHS / United States
R01 CA138818 / CA / NCI NIH HHS / United States
R01 CA142833 / CA / NCI NIH HHS / United States
R01 CA155664 / CA / NCI NIH HHS / United States
R01 CA155664 / CA / NCI NIH HHS / United States
R01 CA158668 / CA / NCI NIH HHS / United States
R01 CA170851 / CA / NCI NIH HHS / United States
R01 CA174929 / CA / NCI NIH HHS / United States
R01 CA174929 / CA / NCI NIH HHS / United States
R01CA114462 / CA / NCI NIH HHS / United States
R01CA142833 / CA / NCI NIH HHS / United States
R01CA158668 / CA / NCI NIH HHS / United States
R01CA170851 / CA / NCI NIH HHS / United States
R21 EB008811 / EB / NIBIB NIH HHS / United States
R21EB008811 / EB / NIBIB NIH HHS / United States
R33 CA183685 / CA / NCI NIH HHS / United States
R33CA183685-01 / CA / NCI NIH HHS / United States
T32 HL007544 / HL / NHLBI NIH HHS / United States
T32HL007544 / HL / NHLBI NIH HHS / United States
U01ES019458 / ES / NIEHS NIH HHS / United States
U54 CA143836 / CA / NCI NIH HHS / United States
U54 CA163155 / CA / NCI NIH HHS / United States
U54CA143836 / CA / NCI NIH HHS / United States
U54CA163155-01 / CA / NCI NIH HHS / United States