The oxytocin receptor signalling system and breast cancer: a critical review

• Published in: Oncogene 2020-09, Vol.39 (37), p.5917-5932
• Main Authors: Liu, Huiping, Gruber, Christian W., Alewood, Paul F., Möller, Andreas, Muttenthaler, Markus
• Format: Article
• Language: English
• Subjects: 38/77; 631/154/555; 631/67/1347; 631/80/304; 631/80/86/2363; 64/60; 82/75; 82/80; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - etiology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer surgery; Cell Biology; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Chemoprevention; Chemotherapy; Contraction; Cytotoxicity; Development and progression; Disease Management; Disease Models, Animal; Disease Susceptibility; Drug Evaluation, Preclinical; Female; G proteins; Gene Expression Regulation, Neoplastic; Human Genetics; Humans; Internal Medicine; Ligands; Mastectomy; Maternal behavior; Medicine; Medicine & Public Health; Membrane proteins; Metastases; Molecular Targeted Therapy; Nervous system; Oncology; Oxytocin; Oxytocin - analogs & derivatives; Oxytocin - metabolism; Oxytocin - pharmacology; Radiation therapy; Receptors, Estrogen - metabolism; Receptors, Oxytocin - genetics; Receptors, Oxytocin - metabolism; Review; Review Article; Sexual behavior; Signal transduction; Signal Transduction - drug effects; Social behavior; Social interactions; Surgery; Therapeutic targets; Tumor cell lines; Tumors; Uterine cancer; Uterus
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-020-01415-8

Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.