• Targeting Metastatic Suppressor Genes: A New Frontier in Cancer Therapy
  • Samane Lotfipour,1,* Abbasali Raz,2 Rosa Jahangiri,3
    1. Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran. Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
    2. Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
    3. Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran. Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran.


  • Introduction: Metastasis suppressor genes (MSGs) are notable for the ability to block the development of metastasis to a secondary organ without affecting the tumor growth at the primary site. This set of genes is defined only by their ability to inhibit metastasis, as they produce proteins of assorted biochemical activities and functions in several different signaling pathways. Also, metastasis suppressors act on different stages of the metastatic process to exert their suppressive effects.
  • Methods: In this review we explored articles about metastatic suppressor genes in google scholar and pubmed data bases.
  • Results: The KISS1, KAI1, MKK4/7, and Nm23-H1 MSGs promote tumor dormancy at metastatic sites, because tumor cells expressing high levels of these MSGs scatter but fail to generate detectable metastases in the secondary organ within the period set for assessing metastasis. Research indicates that KISS1 induces dormancy in isolated metastatic tumor cells by causing these solitary cells to halt growth at the secondary location. KAI1 promotes growth arrest before the cells can extravasate by interacting with a vascular endothelial cell surface marker. MKK4, MKK7, and Nm23-H1 appear to promote dormancy in micrometastatic colonies following numerous cycles of proliferation experienced by the disseminated tumor cells.
  • Conclusion: This review and perspective highlight the evolving comprehension of the critical steps involved in metastatic growth and the contribution of metastasis suppressor proteins in regulating these processes.
  • Keywords: Metastatic suppressor genes, Metastasis inhibition, Gene regulation, Cancer therapeutics, Cancer met