Can diet control cancer development?
Diet, physical inactivity, and obesity may be related to up to 30–35% of cancer deaths. Thus link between diet and cancer has long been investigated by researchers and dietary factors are considered to be having a significant effect on the risk of cancers.
The common belief is that unhealthy diets may contribute to cancer development, while healthy diets may prevent it. Several studies also support this idea. A study published last year, in Medical News Today reported that a low-fat diet supplemented with omega-3 fatty acid may reduce prostate cancer risk. And another study published this week linked a reduction in dietary fibre intake to improved survival rates for women with hormone-unrelated breast cancer.
However the exact mechanism, by which diet influences tumour growth, is still unclear.
A recent study, led by Prof. Roberto Coppari of the Faculty of Medicine at the University of Geneva in Switzerland revealed that conversion from a low- to high-calorie diet appeared to reduce tumour growth when the high-calorie diet was adopted before tumours started to grow. If the switch from a low- to high-calorie diet took place after tumour growth began, it boosted their growth further. Further analysis showed that a change in diet triggered an increase in endoplasmic reticulum (ER) stress. ER regulates protein organization in cells. And a rise in ER stress increases the expression of chaperones, molecules that helps the proteins to function. Moreover too much increase of ER stress leads to cell death, making them unable to spur tumour growth. This may explain why changing to a high-calorie diet reduced tumour growth.
However changing to a high-calorie diet after tumour growth started, may fuel further growth because the tumour cells have already adapted to an increase in ER stress and more stress encourages further tumour cell proliferation.
The team then analyzed the RNA molecules of KRAS driven lung tumours from both low- and high-calorie diet groups and found that switching to a high-calorie diet significantly reduced expression of FKBP10, a chaperone protein specifically expressed in lung cancer cells. FKBP10 deals with increased ER stress by expressing chaperones and not usually found in healthy adults, but in developing embryo and young infants.
The researchers also showed that knockdown of FKBP10 leads to reduced cancer growth. Cancer treatment usually leads to death of both cancer cells and healthy cells. The fact that FKBP10 is expressed only in lung cancer cells and not in healthy ones may form the basis in therapeutic arena. Thus the team is now trying to identify inhibitors of FKBP10 that will hinder cancer cells’ proliferation without damaging the healthy cells. The inhibition of this protein is predicted to have minimal side effects as it is not expressed in cells from a healthy adult.
Diet-Induced Unresolved ER Stress Hinders KRAS-Driven Lung Tumorigenesis. Giorgio Ramadori, Georgia Konstantinidou, Niranjan Venkateswaran, Tommasina Biscotti, Lorraine Morlock, Mirco Galié, Noelle S. Williams, Michele Luchetti, Alfredo Santinelli, Pier Paolo Scaglioni, Roberto Coppari. DOI: http://dx.doi.org/10.1016/j.cmet.2014.11.020
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