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 cancer processes. This process is responsible for about ninety percent of human cancer deaths. Proteins that act to slow or prevent metastases are different from those that act to suppress tumor growth. Genes for about a dozen such proteins are known in humans and other animals.

The treatment of cancer usually aims to destroy and/or stop the growth of the primary tumor. Major improvements in the methods of surgery, radiation and chemotherapy have taken place, but corresponding improvements in patient survival have not always followed. Treatments that focus on the primary cancer typically do not address metastasis.

Metastasis suppressors act by different mechanisms than tumor suppressors and do not affect primary tumors. Tumor suppressors, however, also inhibit metastasis, since metastasis is dependent upon tumorigenicity.

Metastasis suppressors were first identified using microcell-mediated chromosome transfer (MMCT), which introduces chromosomes into intact recipient cells. Chromosomes 1, 6, 7, 8, 10, 11, 12, 16 and 17 harbor metastasis suppressor genes.

MicroRNAs (miRNAs) are a class of gene regulators that bind the 3′ untranslated regions of target messenger RNAs, leading to either suppression of their translation or acceleration of their degradation. In cell MDA-MB-231 and its metastatic variant, six miRNAs displayed lower expression in metastatic cells. Among them, miR-335 and miR-126 suppress metastasis without affecting primary tumor growth. miR-335 targets multiple pathways, including SOX4, MERTK, PTPRN2 and TNC, which contribute to metastasis-suppression. miR-335 expression is correlated with metastasis-free survival in clinical breast cancer.

Metastasis suppressors can potentially serve as prognostic markers, therapeutic targets and predictors for treatment response.

High NM23 expression is correlated with good prognosis in multiple tumor types, including breast cancer. KAI1, PEBP1 and RECK expression correlate with improved survival in multiple tumor types, including colorectal cancer. High expression of CTGF is correlated with improved survival in colorectal cancer, non-small cell lung carcinoma and gallbladder cancer, but the correlation is reversed in esophageal cancer and glioma.

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