17.10: Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter cells and all the future daughter cells. Such abnormal cell proliferation defines the characteristic of what we call cancer. The best example to explain this condition is the mutation in the Ras and MYC proteins.
Normal Ras proteins are GTPases that function in signal transduction from cell surface receptors to the cell’s interior. Ras proteins can be denoted as the binary switches that cycle between ON and OFF states during cellular growth. Usually, these switches are tightly regulated, but in Ras-related diseases such as cancer, the Ras gene mutation or their regulator renders Ras proteins persistently active. For instance, a single amino acid missense mutation in the K-Ras protein (a type of Ras protein) impairs its normal functioning. The mutant K-Ras cannot be inactivated, leading to continuous growth stimulation. K-Ras mutation occurs in 15%- 20% of human cancers, and is most commonly seen in colon cancer, lung cancer, pancreatic cancer, and leukemia.
Abnormal cell proliferation can also occur when mutation results in overexpression of MYC protein. The MYC oncogene belongs to a family of "super-transcription factors" and is deregulated in more than 50% of human cancers. The MYC affects a spectrum of cellular functions, including protein translation, cell cycle progression, ribosome biosynthesis, cell proliferation, differentiation, survival, and immune surveillance.
