Semin Reprod Med 2019; 37(04): 197-206
DOI: 10.1055/s-0039-3400968
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

KISS1/KISS1R and Breast Cancer: Metastasis Promoter

Stephania Guzman
1  Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
,
Muriel Brackstone
2  Department of Surgery, London Health Sciences Centre, London, Ontario, Canada
,
Frederic Wondisford
1  Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
,
Andy V. Babwah
3  Department of Pediatrics, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
4  Child Health Institute of New Jersey, New Brunswick, New Jersey
,
Moshmi Bhattacharya
1  Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
4  Child Health Institute of New Jersey, New Brunswick, New Jersey
5  Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey
› Author Affiliations
Further Information

Publication History

Publication Date:
23 January 2020 (online)

Abstract

Kisspeptins (KPs), peptide products of the kisspeptin-1 (KISS1) gene, are the endogenous ligands for the KISS1 receptor, KISS1R, which is a G protein-coupled receptor. In many human tumors, KISS1 functions as a metastasis-suppressor gene and KISS1/KISS1R signaling has antimetastatic and tumor-suppressor roles. On the contrary, emerging evidence indicates that the KP/KISS1R pathway plays detrimental roles in triple negative breast cancer (TNBC), the most difficult type of breast cancer to treat. TNBC patients initially respond to chemotherapy, but tumors acquire drug resistance and many patients relapse and die of metastases within a few years. In this review, we summarize recent developments in the understanding of the mechanisms by which KP/KISS1R signaling plays an adverse role in TNBC. This includes focusing on how KISS1R signaling regulates the cell cytoskeleton to induce tumor invadopodia formation and how KISS1R communicates with growth factor receptors such as the epidermal growth factor receptor, the receptor tyrosine kinase AXL, and transforming growth factor-β to promote cell invasion, metastasis, and drug resistance.