Redox and metabolic reprogramming in breast cancer and cancer‐associated adipose tissue

Abstract

Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer‐associated adipose tissue (CAAT). Understanding how the redox‐metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo‐organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell‐specific redox‐metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.

The Role of Oxidative Stress in Tumorigenesis and Progression

“…Cancer cells also possess more powerful antioxidant defenses in contrast to its multitudes of ROS [ 26 ]. Intensive ROS scavenging, including peroxiredoxin 1 (PRDX1) [ 27 ], SOD2 [ 28 ], CAT, GSH-PXs, thioredoxins (TRXs), and GSH, can be upregulated by the activation of TNFα , Nrf2 , HIF1α , AMPK , and PGC1α , protecting cancer cells from damage and subsequent cell death [ 29 , 30 ]. Furthermore, NADPH, which is perceived as a pivot in the antioxidant system, with the capacity of renewing reduced glutathione (GSH) and thioredoxin (TRX), is drastically produced in cancer cells via fostering the pentose phosphate pathway, malic enzymes, one-carbon metabolism, etc.…”

Phytoestrogens as estrogen receptor ligands

“…Although ERα and ERβ are mediating multiple biological effects in a similar manner, their actions are sometimes resulting in entirely opposing effects. Namely, ERs are modulators of cell growth and differentiation but ERα stimulates cell growth and proliferation, while ERβ is associated with cell differentiation and tumor suppression [59]. On the other hand, both ERα and ERβ are equally effective in transcriptional repression of inflammatory genes responsible for osteoporosis [60] and other beneficial ER effects.…”