Abstract
Simple SummaryCirculating hormones and their specific receptors play a significant role in the development and progression of various cancers. This review aimed to summarize current knowledge about the dopamine D1 receptor’s biological role in different cancers, including breast cancer, central nervous system tumors, lymphoproliferative disorders, and other neoplasms. Treatment with dopamine D1 receptor agonists was proven to exert a major anti-cancer effect in many preclinical models. We highlight this receptor’s potential as a target for the adjunct therapy of tumors and discuss possibilities and necessities for further research in this area.Dopamine is a biologically active compound belonging to catecholamines. It plays its roles in the human body, acting both as a circulating hormone and neurotransmitter. It acts through G-protein-coupled receptors divided into two subgroups: D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D3R, D4R). Physiologically, dopamine receptors are involved in central nervous system functions: motivation or cognition, and peripheral actions such as blood pressure and immune response modulation. Increasing evidence indicates that the dopamine D1 receptor may play a significant role in developing different human neoplasms. This receptor’s value was presented in the context of regulating various signaling pathways important in tumor development, including neoplastic cell proliferation, apoptosis, autophagy, migration, invasiveness, or the enrichment of cancer stem cells population. Recent studies proved that its activation by selective or non-selective agonists is associated with significant tumor growth suppression, metastases prevention, and tumor microvasculature maturation. It may also exert a synergistic anti-cancer effect when combined with tyrosine kinase inhibitors or temozolomide. This review provides a comprehensive insight into the heterogeneity of dopamine D1 receptor molecular roles and signaling pathways in human neoplasm development and discusses possible perspectives of its therapeutic targeting as an adjunct anti-cancer strategy of treatment. We highlight the priorities for further directions in this research area.
Highlights
Dopamine (DA) exerts its major functions in organisms, acting both as a neurotransmitter in the central nervous system and as a circulating hormone in the periphery
The dysregulation of the dopaminergic system is a fundamental mechanism of many diseases, including Parkinson’s disease, schizophrenia [9], hypertension and metabolic dysfunctions [10] or gut motility abnormalities [11]
From the perspective of rapidly widening literature regarding the value of dopamine receptors in cancer pathogenesis, we reviewed the current knowledge about the activity and signaling mechanisms of D1 receptor (D1R) in different cancers
Summary
Dopamine (DA) exerts its major functions in organisms, acting both as a neurotransmitter in the central nervous system and as a circulating hormone in the periphery. Peripheral synthesis of this compound can occur in adrenal glands, spleen, pancreas, and sympathetic nerves [1,2]. Cognition [6], while peripherally influencing kidney functions [7], blood pressure regulatory mechanisms [7], and even immunological response in humans [8]. Cancers 2020, 12, 3232 receptors (DRs) was described in a wide range of tissues and organs such as the brain, retina, heart, coronary arteries, gastrointestinal tract, and sympathetic ganglia [9]. The dysregulation of the dopaminergic system is a fundamental mechanism of many diseases, including Parkinson’s disease, schizophrenia [9], hypertension and metabolic dysfunctions [10] or gut motility abnormalities [11].
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