Hallmarks of Malignant Growth: Evading Growth SuppressorsJune 1, 2018
In trying to understand what makes continuous growth such a powerful idea (despite clear evidence that it often becomes harmful) The Incredible Shrinking Man turned to cancer research to learn where healthy growth turns malignant. Although cancer is a very complex phenomenon the seminal paper “ The hallmarks of cancer” managed to simplify its underlying process to ten common traits that every single cancer shares to facilitate the transformation from a normal cell to a cancer cell. Published by Robert Weinberg and Douglas Hanahan in 2000, with an updated version in 2013, the paper functions as a guide and lens to learn what the underlying principles of growth are. And what to do about it when things go wrong.
The second hallmark described by the authors is the ability of cancer cells to evade growth suppressors. Growth suppressors are proteins that inhibit growth by inducing a cell into a quiescent (G0) or post-mitotic state. The growth of normal cells is kept under control by growth inhibitors in the surrounding environment, in the extracellular matrix and on the surface of neighboring cells. Cancer must target this system to continue its uncontrolled replication. Cancers biggest regulatory adversary in this process is retinoblastoma, a growth suppressor that binds to and inactivates proteins involved in cell replication. Retinoblastoma in return can be switched on or off in response to antigrowth signals in its microenvironment. There are several ways in which cancer cells disrupt the work of these antigrowth signals: 1. Some cancer cells stop responding to antigrowth signals altogether by producing less receptors on their cell surface. 2. In some cancer cells the receptor is mutated so that they cannot respond to the presence of antigrowth factors. 3. Some cancers get rid of downstream proteins that respond to antigrowth signalling. 4. Retinoblastoma protein itself, the end target of antigrowth signalling, can be lost through mutation of its gene. 5. Some oncoproteins can block the function of retinoblastoma.