Metastasis suppressor

A metastasis suppressor is a protein that acts to slow or prevent metastases (secondary tumors) from spreading in the body of an organism with cancer. Metastasis is one of the most lethal attributes of cancer. This attribute is responsible for about ninety percent of human cancer deaths.[1] These proteins that act to slow or prevent metastases are different from ones that act to suppress tumor growth. Genes for about a dozen such proteins are known in humans and other animals.[2]

Background

The treatment of cancer has usually been aimed at destroying the primary tumor or at least in stopping its growth. Even though major improvements in the methods of surgery, radiation, and chemotherapy have taken place, often enough there have not been corresponding improvements in patient survival. Treatment methods that focus on the primary cancer typically fall short in aiding the patient after the cancer has metastasized.[1]

Metastasis suppressors act by different mechanisms than tumor suppressors, and they have no effect on primary tumors. Tumor suppressors, however, also block metastasis, since metastasis is dependent upon tumorigenicity.[1]

Eight metastasis suppressors have been identified, and most act by altering aspects of signal transduction. NM23 is a suppressor active in melanoma, breast and colon cancers, and apparently inhibits the functioning of a kinase enzyme that promotes cell division. MKK4 is a suppressor active in prostate and ovarian cancers, and apparently functions by facilitating apoptosis, or death of abnormal cells such as cancer cells. KAI1 is found in prostate and breast cancers, and forms complexes with proteins called integrins. Integrins are one of the structures that link cells together, and the complex formation may inhibit detachment and migration of the cancer cells. BRMS1 promotes the activity of the gap junctions of cells. The gap junctions are found on the cell membranes and allow for chemical and electrical communication between cells. It has been proposed that this communication between metastic tumor cells might contribute to inhibition of metastic growth. KISS1 is found in melanoma and breast cancers, and acts by synthesizing a protein receptor. RHOGD12 is active in bladder cancer, and inhibits proteins that aid in cancer cell migration. CRSP3 and VDUP1 are both active in melanoma. CRSP3 is a co-activator of genes involved in cancer growth, while VDUP1 inhibits a protein involved in cell proliferation.[1]

Impact

Metastasis suppressor genes may offer valuable mechanistic insight for guiding specific therapeutic strategies, which may include drug-induced reactivation of metastasis suppressor genes and their signaling pathways. Clinical assessment of metastasis suppressor gene product status in disseminated cancer cells may improve the accuracy of predicting the prognosis in patients with clinically localized disease.[3] Before any new treatments are implemented for general use, doctors conduct studies to find out whether the treatment is both safe for patients and effective against the disease. The results of such studies will ultimately provide the answers needed to continue work on antimetastasis drug development. Future studies should however, focus on treatment at the secondary tumor sites. This is a method to make progress in fighting cancer.[2] These proteins are different from ones that act to suppress tumor growth.[4] Genes for about a dozen such proteins are known in humans and other animals, including BRMS1, CRSP3, DRG1, KAI1, KISS1, NM23, and various TIMPs.[5][6]

References

  1. ↑ 1.0 1.1 1.2 1.3 Olle, David (September 9, 2009). "Metastasis Suppressors". Suite 101.
  2. ↑ 2.0 2.1 Sobel, Mark E. (1990). "Metastasis Suppressor Genes". Journal of the National Cancer Institute 82 (4): 267–76. doi:10.1093/jnci/82.4.267. PMID 2405170.
  3. ↑ Kauffman, Eric C.; Robinson, Victoria L.; Stadler, Walter M.; Sokoloff, Mitchell H.; Rinker-Schaeffer, Carrie W. (2003). "Metastasis Suppression: The Evolving Role of Metastasis Suppressor Genes for Regulating Cancer Cell Growth at the Secondary Site". The Journal of Urology 169 (3): 1122–33. doi:10.1097/01.ju.0000051580.89109.4b. PMID 12576866.
  4. ↑ Yoshida, Barbara A.; Sokoloff, Mitchell M.; Welch, Danny R.; Rinker-Schaeffer, Carrie W. (2000). "Metastasis-Suppressor Genes: a Review and Perspective on an Emerging Field". Journal of the National Cancer Institute 92 (21): 1717–30. doi:10.1093/jnci/92.21.1717. PMID 11058615.
  5. ↑ Shevde, Lalita A.; Welch, Danny R. (2003). "Metastasis suppressor pathways—an evolving paradigm". Cancer Letters 198 (1): 1–20. doi:10.1016/S0304-3835(03)00304-5. PMID 12893425.
  6. ↑ Jackson, Paul, ed. (2007). New Developments in Metastasis Suppressor Research. New York: Nova Science Publishers. ISBN 978-1-60021-603-9.

Further reading