New Insights into the Role of Exercise in Inhibiting mTOR Signaling in Triple‐Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 and is characterized by its aggressive nature, lack of targets for targeted therapies, and early peak of recurrence. Due to these specific characteristics, chemotherapy does not usually yield substantial improvements and new target therapies and alternative strategies are needed. The beneficial responses of TNBC survivors to regular exercise, including a reduction in the rate of tumor growth, are becoming increasingly apparent. Physiological adaptations to exercise occur in skeletal muscle but have an impact on the entire body through systemic control of energy homeostasis and metabolism, which in turn influence the TNBC tumor microenvironment. Gaining insights into the causal mechanisms of the therapeutic cancer control properties of regular exercise is important to improve the prescription and implementation of exercise and training in TNBC survivors. Here, we provide new evidence of the effects of exercise on TNBC prevention, control, and outcomes, based on the inhibition of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB also known as Akt)/mammalian target of rapamycin (mTOR) (PI3K-Akt-mTOR) signaling. These findings have wide-ranging clinical implications for cancer treatment, including recurrence and case management.

Effect of Physical Training on the Levels of Sex Hormones and the Expression of Their Receptors in Rats With Induced Mammary Cancer in Secondary Prevention Model – Preliminary Study

“…Many scientific reports indicate a protective effect of physical activity on breast cancer (8,9,13,(15)(16)(17), including in patients after comprehensive breast cancer treatment (8,9,(18)(19)(20)(21)(22)(23)(24). From the results of our study, we found two mechanisms which confirm these observations, namely desensitization of cells due to reduced expression of ER and PR, as well as increased apoptosis which positively correlated with the level of training intensity.…”

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

“…54,55 With some cancers, it is generally accepted that autophagy can suppress tumor initiation and cancer growth; and since autophagy blocks growth and increases breakdown of proteins, this is quite logical. 56,57 (Cuervo, 2004(Cuervo, , 2008. Cancer cells often have much lower levels of basal autophagy than normal cells.…”

“…In certain cancers, mTORC1 inhibitors have demonstrated anticancer effects (Table 1). 56 Metformin, a drug widely used in type 2 diabetes, also activates autophagy but not directly through the mTORC1 system (Table 1). 72 This drug increases AMPK, a protein molecule that signals the energy status of the cell (Figure 2).…”

Impact of Exercise on Immunometabolism in Multiple Sclerosis

“…Moreover, through PGC-1 α phosphorylation, aerobic exercise influences other transcription factors, like peroxisome proliferator-activated receptor- γ (PPAR γ ), as well as estrogen-related receptors, ERR α and ERR γ , which control mitochondrial energy metabolism via the tricarboxylic acid (TCA) cycle, FAO, and oxidative phosphorylation [ 149 , 150 ]. Endurance and, to a lesser extent, resistance exercises have been shown to activate AMPK, and inhibit mTOR in non-muscular tissues as well, such as liver and fat [ 151 ]. This leads us to surmise that this metabolic setting also works synergistically with the immune system, which has its proinflammatory phenotype aggravated in states of overfeeding and nutrient excess, triggering chronic low-grade inflammation, and in states of fasting and exercise, an anti-inflammatory state.…”