The reverse Warburg Effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts

Using the “reverse Warburg effect” to identify high-risk breast cancer patients

“…Similarly, 58 patients showed high levels of Cav-1 stromal mitophagy and aerobic glycolysis, due to increased oxidative stress. [11][12][13][14][15] Virtually identical catabolic processes and associations with aerobic glycolysis were identified via analysis of laser-captured tumor stroma from human breast cancer patients lacking stromal Cav-1. 16 This led to the proposal of a novel two-compartment model of tumor metabolism, termed the "reverse Warburg effect."…”

Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis

“…26,75,76 Most importantly, Cav-1-deficient fibroblasts promote tumor growth up to ~4-fold, when co-injected with MDA-MB-231 triple negative human breast cancer cells. 77,78 Cav-1-deficent fibroblasts and hydrogen peroxide treated fibroblasts also share the same proteomic profile, with the upregulation of myofibroblast markers, glycolytic enzymes and anti-oxidant proteins. 22,74,[78][79][80] Consistent with these findings, a loss of stromal Cav-1 is a powerful biomarker for a lethal tumor microenvironment, in breast and prostate cancers.…”

“…77,78 Cav-1-deficent fibroblasts and hydrogen peroxide treated fibroblasts also share the same proteomic profile, with the upregulation of myofibroblast markers, glycolytic enzymes and anti-oxidant proteins. 22,74,[78][79][80] Consistent with these findings, a loss of stromal Cav-1 is a powerful biomarker for a lethal tumor microenvironment, in breast and prostate cancers. 37,[81][82][83][84][85][86][87][88][89] More specifically, in breast cancer patients, a loss of stromal Cav-1 is associated with early conditions, most of the DNA damage occurs in the cancer-associated fibroblasts, as the MCF7 cancer cells effectively mount an anti-oxidant defense by upregulating key proteins, such as peroxiredoxin-1 and TIGAR.…”

Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism

“…22,[37][38][39][40] In turn, these nutrients stimulated mitochondrial biogenesis, OXPHOS and autophagy resistance in the epithelial cancer cells and protected the cancer cells against basal and chemotherapy-induced apoptosis. 33,34,[41][42][43][44][45] Thus, two-compartment tumor metabolism and mitochondrial "health" may be the basis of chemoresistance and therapy failure in cancer patients. 23,46 Given that two-compartment tumor metabolism may be a clinical barrier to effective cancer treatments, normalizing energy balance (homeostasis) should cut off the fuel supply to cancer cell mitochondria (Fig.…”