The stress connection in cancer: the adrenergic fuelling of breast tumors

Abstract

Cancer progression involves complex interactions between tumor cells and the surrounding microenvironment. Chronic psychosocial stress and sympathetic nervous system activation lead to abnormal catecholamine release, impacting tumor cells directly and indirectly and fuelling cancer-promoting effects. However, the same adrenergic Receptor (AR) that mediate these effects could also convey exercise-related beneficial changes. Epidemiological studies show conflicting associations between stress, AR inhibitors, and breast cancer (BC) metastatic progression. Adrenergic sympathetic stress triggers sustained inflammatory and hypoxic-related signaling pathways, alters function and distribution of immune cell populations, and remodels blood vessels, leading to immunosuppression and premetastatic site formation. Activated AR initiate feedback loops with tyrosine kinase receptors and chemokine receptors, affecting stem-related transcription factors, pro-inflammatory mediators, angiogenic factors, and energy metabolism regulators, promoting tumor growth and invasion. Understanding molecular mechanisms of agonistic and antagonistic AR ligands and crosstalk with other signaling pathways is crucial for developing effective therapies targeting adrenergic-driven BC progression.