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.
Keywords
kisspeptin - KISS1R - triple negative breast cancer - metastasis - tumor invasion
