How Tumor Cells Survive Dietary Restriction
A Genetic Modification Allows Cancerous Cells to Survive Starvation
Jun 2, 2009
Scientific studies suggest that environmental factors associated with the Western life-style promote the development of cancer. One such factor that has been implicated is the dietary fat contained in junk food. In the same line of thinking, epidemiologists have suggested that calorie-restricted diets may protect against cancer and slow tumor growth, however some discrepancies have been noticed among different experiments. A new study published in the scientific journal Nature of April 2009 reveals why the measure works only in some types of tumors but not the others (Nature, vol458, pp725-731, 2009)
Dietary Restriction and Cancer
For several decades it was known that diet prolongs the life of animals (for example, rodents), and that dietary restriction may also protect the frequency of cancer such as skin cancer, breast cancer or lymphoma. Obesity and diabetes are also associated with a higher risk of cancer in humans, particularly colorectal, post-menopausal breast, endometrial, pancreatic, advance prostate, hepatocellular, gallbladder, kidney and esophageal cancers.
Interestingly, researchers have also noticed that dietary restriction does not systematically reduce the growth of tumors inoculated in mice. Fractions of tumor from the same organ can show a different response to dietary restriction and may become insensitive to this treatment. However the reason for that was not understood.
Molecular Mechanism Linked to Dietary Restriction Resistance
A new study entitled “ Tumours with PI3K activation are resistant to dietary restriction” identifies a molecular mechanism responsible for the resistance of tumor cells to dietary restriction. The study was published in April 2009 in the famous scientific journal Nature by Nada Y Kalaany and Dr David M Sabatini from the Whitehead Institute and Massachusetts Institute of Technology (Cambridge, MA).
PI3K and Akt Signaling Pathway
In their study, Kalaany and Dr Sabatini investigated the role of a protein called phosphoinositide 3-kinase or PI3K. PI3K is already well known as a regulator of cell growth. While PI3K was also associated with the survival of tumor cells, it has not been linked to reduction of tumor growth in a condition of dietary restriction. In cells stimulated by the growth factor insulin, PI3K modifies other proteins called Akt, engaging a molecular process know as signaling cascade. A signaling cascade is a cascade of protein modification leading to the activation of cellular targets and specific gene expression.
Genetic Mutations and Sensitivity to Dietary Restriction
By comparing tumor cells which are sensitive to dietary restriction with tumor cells that are not sensitive to dietary restriction, the investigators noticed that the PI3K and Akt signaling cascade was activated in resistant cells. In addition, the investigators found genetic mutations in the PI3K gene and deletion in PTEN gene, a regulator of PI3K protein. Such mutations lead to the activation of PI3K/Akt cascade without the need of insulin.
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