KISS1 metastasis suppression and emergent pathways.
Metastatic disease is the most critical impediment to cancer patient survival. However, comparatively little is known concerning the intricate pathways which govern the complex phenotypes associated with metastasis. The KISS1 metastasis suppressor gene inhibits metastasis in both in vivo melanoma and breast carcinoma models. Despite its clear physiological activity, the mechanism of KISS1 remains unclear. Recent identification of a 54 amino acid peptide of KISS1, termed metastin or kisspeptin-54, and its cognate G-protein coupled receptor (hOT7T175, AXOR12, GPR54) have provided additional clues and avenues of research. While studies have attributed KISS1 with modulation of NFkappaB regulation, experiments with metastin and its receptor implicate MAP kinase pathways and also suggest the potential of autocrine, paracrine and endocrine roles. Impacts on motility, chemotaxis, adhesion and invasion have each been documented in disparate cell lines and conflicting observations require resolution. Nevertheless, mounting clinical evidence, particularly the loss of KISS1 in metastases, correlates KISS1 and metastin receptor expression with human tumor progression. Together, the data substantiate roles for these molecules in metastasis regulation.
Harms
John F
JF
Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Welch
Danny R
DR
Miele
Mary E
ME
D001943:Breast Neoplasms / Q000235:genetics; D002896:Chromosomes, Human, Pair 6; D016147:Genes, Tumor Suppressor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D059648:Kisspeptins; D048670:MAP Kinase Kinase 4; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000502:physiology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D025521:Tumor Suppressor Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases