Title:Molecular Mechanisms Underlying Psychological Stress and Cancer
Volume: 22
Issue: 16
Author(s): Kyeong Jin Shin, Yu Jin Lee, Yong Ryoul Yang, Seorim Park, Pann-Ghill Suh, Matilde Yung Follo, Lucio Cocco and Sung Ho Ryu
Affiliation:
Keywords:
Psychological stress, cancer, tumor microenvironment, adrenergic receptor, catecholamine, anticancer drug.
Abstract: Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected
problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular
disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association
between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients.
Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via
the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS).
These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer
therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways
through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation
and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and
its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their
cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal
cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.