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Updated: Jul 15, 2026

Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
Published on: September 4, 2011
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor
T Ohtaki1, Y Shintani, S Honda
1Pharmaceutical Discovery Research Division, Takeda Chemical Industries Ltd, Wadai 10, Tsukuba, Ibaraki 300-4293, Japan. Ohtaki_Tetsuya@takeda.co.jp
Abstract:
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.
Insights
The KiSS-1 gene product, metastin, suppresses cancer metastasis by inhibiting cell invasion and spread. This discovery offers a potential new therapeutic strategy for treating metastatic cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastasis is a primary cause of cancer mortality, involving complex cellular processes.
- The human KiSS-1 gene is known to suppress metastasis in melanoma and breast cancer but its product and mechanism remain unclear.
Purpose of the Study:
- To identify the KiSS-1 gene product and elucidate its functional mechanisms in metastasis suppression.
Main Methods:
- Isolation and characterization of the KiSS-1 gene product from human placenta.
- Identification of the product as the endogenous ligand for the orphan G-protein-coupled receptor hOT7T175, named metastin.
- In vitro assays assessing metastin's effect on chemotaxis and invasion in transfected cells.
- In vivo studies evaluating metastin's impact on pulmonary metastasis in melanoma models.
Main Results:
- The KiSS-1 gene encodes a 54-amino-acid peptide, metastin.
- Metastin inhibits chemotaxis and invasion of hOT7T175-transfected cells in vitro.
- Metastin attenuates pulmonary metastasis in vivo in a melanoma model.
Conclusions:
- Metastin, the KiSS-1 gene product, acts as a metastasis suppressor.
- The findings suggest potential therapeutic strategies targeting the metastin/hOT7T175 pathway for cancer treatment.
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