Metastasis suppressor
Encyclopedia
A metastasis suppressor is a protein that acts to slow or prevent metastases (secondary tumor
s) 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 (Olle, David. "Metastasis Suppressors." Suite 101. Web. 05 Oct. 2009.). 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 (Sobel, ME. 1990. Metastasis suppressor genes. Journal of the National Cancer Institute 82: 267-276.).
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, all 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 (Olle, David. "Metastasis Suppressors." Suite 101. Web. 05 Oct. 2009.).
Metastasis suppressors act by different mechanisms than tumor suppressors, and have no effect on primary tumors. Tumor suppressors, however, also block metastasis, since metastasis is dependent tumorigenicity (Suite 101. Web. 05 Oct. 2009.). 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 junction
s 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 (Olle, David. "Metastasis Suppressors.").
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 ("Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site." NCBI, Mar. 2003.). 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 how we will make progress in fighting this disease. These proteins are different from ones that act to suppress tumor growth
. Genes for about a dozen such proteins are known in humans and other animals, including BRMS1
, CRSP3
, DRG1
, KAI1, KISS1, NM23, and various TIMPs.
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s) from spreading in the body of an organism with cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Metastasis is one of the most lethal attributes of cancer. This attribute is responsible for about ninety percent of human cancer deaths (Olle, David. "Metastasis Suppressors." Suite 101. Web. 05 Oct. 2009.). 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 (Sobel, ME. 1990. Metastasis suppressor genes. Journal of the National Cancer Institute 82: 267-276.).
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, all 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 (Olle, David. "Metastasis Suppressors." Suite 101. Web. 05 Oct. 2009.).
Metastasis suppressors act by different mechanisms than tumor suppressors, and have no effect on primary tumors. Tumor suppressors, however, also block metastasis, since metastasis is dependent tumorigenicity (Suite 101. Web. 05 Oct. 2009.). 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 junction
Gap junction
A gap junction or nexus is a specialized intercellular connection between a multitude of animal cell-types. It directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells....
s 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 (Olle, David. "Metastasis Suppressors.").
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 ("Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site." NCBI, Mar. 2003.). 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 how we will make progress in fighting this disease. These proteins are different from ones that act to suppress tumor growth
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
. Genes for about a dozen such proteins are known in humans and other animals, including BRMS1
BRMS1
Breast cancer metastasis-suppressor 1 is a protein that in humans is encoded by the BRMS1 gene.-Further reading:...
, CRSP3
CRSP3
Mediator of RNA polymerase II transcription subunit 23 is an enzyme that in humans is encoded by the MED23 gene.-Interactions:CRSP3 has been shown to interact with Estrogen receptor alpha, CEBPB and Cyclin-dependent kinase 8.-Further reading:...
, DRG1
DRG1
Developmentally-regulated GTP-binding protein 1 is a protein that in humans is encoded by the DRG1 gene.-Further reading:...
, KAI1, KISS1, NM23, and various TIMPs.