Tumor Suppressor Proteins


 Tumor Suppressor Proteins Background

Cancer is caused by catastrophic failure of numerous cellular processes. The progression from normal cell to cancer cell is a multi-step process involving functional alterations in a series of key regulatory proteins which can occur due to genetic mutations, alterations in gene expression or due to the activity of infectious agents (e.g., human papilloma virus). Genes that encode proteins that activate cell proliferation are often up-regulated in cancer via overexpression or by mutations that cause the resulting protein to be constitutively active. These cancer promoting genes are called oncogenes. Their negative regulatory counterparts, genes that encode proteins that prevent cancer from forming, are called tumor suppressors. Cancers grow unchecked once these tumor suppressors are lost by mutation, hyper-phosphorylation, or promoter methylation.
There have been more than 70 tumor suppressors identified to date of varying importance. Some are lost late in tumorigenesis and are considered to be 'passenger mutations,' those that confer little or no survival advantage to an existing cancer. Other tumor suppressors are lost at the incipient stages of tumor neogenesis, this loss being crucial for the evolution from normal cell to cancer cell. These 'driver mutations' occur in tumor suppressors that act as sentinels, each protecting the integrity of cellular processes crucial to maintaining a normally functioning cell. These are the major tumor suppressors.
For example, 'sustaining proliferative signaling' is quintessentially what makes cancer such a deadly disease. All of the other hallmarks support this unrestricted cellular proliferation in some way. While this is a hallmark generally driven by oncogenes, a tumor suppressor that acts as a guardian against uncontrolled growth is the phosphatase and tensin homolog (PTEN). PTEN acts as a negative regulator of the AKT pathway serving to dephosphorylate PIP3 into PIP2, thereby repressing AKT, signaling to the cell to stop dividing. Befitting of its status as a major tumor suppressor, PTEN is also involved in regulation of apoptosis, migration, adhesion, and genetic stability. It is commonly lost in many human cancers including 30-70% of prostate cancer.
'Activating invasion and metastasis' is the multi-step process by which epithelial cells acquire the ability to invade adjacent tissues and eventually disseminate to distal sites setting up distant metastases. This process begins with a series of steps known as the epithelial-to-mesenchymal transition (EMT), controlled by the next major tumor suppressor, transforming growth factor β (TGFβ). TGFβ acts as a tumor suppressor in the early stages of tumorigenesis, serving to maintain a favorable cytokine and chemokine profile in the tumor microenvironment. However, as the disease progresses, oncogenes can serve to convert TGFβ function to induce EMT leading to increased invasion and migration. As such, TGFβ acts as both a major tumor suppressor, and at advanced stages of disease, an oncogene.
Creative Biomart provides kinds of tumor suppressors of several sources, grades and formulations for your research applications.