Mechanisms that maintain telomere length play a permissive role in allowing cancer cells to continue dividing but they do not actually cause cells to divide. The abnormalities that drive the ongoing proliferation of cancer cells can be traced to defects in the various signalling mechanisms that control cell division. 

Cell proliferation is normally regulated by extra-cellular growth factors that bind to cell surface receptors and activate signalling pathways within the targeted cells. Normal cells do not proliferate unless they are stimulated by an appropriate growth factor but this restraining mechanism is circumvented in cancer cells by defects that create a constant signal to divide.

Disruptions in cell-cycle control also contribute to the unrestrained proliferation of cancer cells. The commitment to proceed through the cell cycle is made at the restriction point, which controls progression from Gl into S phase. If normal cells are grown under sub-optimal conditions (for example, insufficient growth factors, high cell density, lack of anchorage, or inadequate nutrients), the cells become arrested at the restriction point and stop dividing. 

In comparable situations, cancer cells continue to proliferate; if conditions are extremely adverse, as occurs with extreme nutritional deprivation, they eventually die at random points in the cell cycle rather than arresting in Gl. The reason for this abnormal behaviour is that cell-cycle controls do not function properly in cancer cells. Besides failing to respond appropriately to external signals, cancer cells are also unresponsive to internal conditions, such as DNA damage, that would normally trigger checkpoint mechanisms.

Another factor that influences the growth of cancer cells is the rate at which they die. If the normal mechanisms for triggering cell death are disrupted, proliferating cells will accumulate faster than they would normally do. The control of cell death is exerted largely through pathways that trigger apoptosis to get rid of unnecessary or defective cells. 

Since cancer cells fit the classic definition of unnecessary or defective cells — that is, they grow in an uncontrolled fashion and exhibit DNA and chromosomal damage — why aren’t they killed by apoptosis? The answer is that cancer cells have various ways of blocking the pathways that trigger apoptosis and that allows them to survive and proliferate under conditions that would otherwise cause cell death.

Uncontrolled cell proliferation is a complex trait that arises from failures in growth signalling pathways, cell-cycle controls and apoptosis. The molecular defects responsible for such failures are the kind of gene mutations that lead to cancer.

Tapan Kumar Maitra

THE WRITER IS ASSOCIATE PROFESSOR, HEAD, DEPARTMENT OF BOTANY, ANANDA MOHAN COLLEGE, KOLKATA, AND ALSO FELLOW, BOTANICAL SOCIETY OF BENGAL, HE CAN BE CONTACTED AT  tapanmaitra59@yahoo.co.in