Numerous studies have linked high-calorie diets to increased risk of cancer. But in a new study, researchers have found that switching from a low- to high-calorie diet can either encourage tumor growth or reduce it.
The association between diet and cancer has long been investigated by researchers. The general consensus is that unhealthy diets may contribute to cancer development, while healthy diets may prevent it.
Last year, for example, Medical News Today reported on a study suggesting that a low-fat diet supplemented with omega-3 may reduce prostate cancer risk. And another study published this week linked a reduction in dietary fat intake to improved survival rates for women with hormone-unrelated breast cancer.
But the team involved in this latest study – led by Prof. Roberto Coppari of the Faculty of Medicine at the University of Geneva in Switzerland – notes that the mechanisms by which diet influences tumor growth is unclear, and this is something they set out to investigate.
Specifically, the researchers focused on tumors driven by mutations in the KRAS gene, which are often found in lung, pancreas and colon cancers.
Prof. Coppari and his team wanted to see how switching from a diet low in calories to a high-calorie diet affects tumor growth in the lungs.
The results of the study – published in the journal Cell Metabolism – revealed that conversion from a low- to high-calorie diet appeared to reduce tumor growth when the high-calorie diet was adopted before tumors started to grow. If the switch from a low- to high-calorie diet took place after tumor growth began, it boosted their growth further.
On further analysis, the team found that a change in diet triggered an increase in stress in the endoplasmic reticulum – an area in cells that regulates protein organization. A rise in stress in this area increases expression of chaperones, which are molecules that aid protein function.
The researchers note that too much of a stress increase in the endoplasmic reticulum can cause cells to die, making the cells unable to spur tumor growth. This may explain why changing to a high-calorie diet reduced tumor growth.
The team says changing to a high-calorie diet after tumor growth started, however, may fuel further growth because the tumor cells have already adapted to an increase in endoplasmic reticulum stress; more stress encourages further tumor cell proliferation.
Commenting on their findings, co-first study author Giorgio Ramadori, of the University of Geneva, says:
“Our study does not show that, by eating junk food, people would be protected from lung cancer. But the high-calorie diet helped us discover a very specific molecular mechanism required for lung tumor cells to proliferate that could pave the way for new therapeutic approaches.”
By analyzing the RNA molecules of lung tumors from both low- and high-calorie diet groups, the team found that switching to a high-calorie diet significantly reduced expression of a chaperone protein called FKBP10, which was only found in lung cancer cells.
The researchers explain that FKBP10 is not usually found in healthy adults, but it can be found in the developing embryo and young infants; it deals with increased endoplasmic reticulum stress by expressing chaperones.
After human development is complete, however, endoplasmic reticulum stress reduces, meaning chaperone expression is no longer required. The fact FKBP10 was found in lung cancer cells means it is likely there to deal with a rise in endoplasmic reticulum stress once again.
Prof. Coppari and his team note that cancer treatment usually leads to death of both cancer cells and healthy cells. But they say that blocking FKBP10 could impair cancer cell proliferation without killing healthy cells, offering a potential new strategy to treat cancer patients.
Prof. Coppari explains:
“In this study we show that knockdown of FKBP10 leads to reduced cancer growth. Human lung cancer cells express FKBP10 while the nearby healthy lung tissue does not; this is very interesting and appealing to eventually translate these findings to the clinical arena.
Hence, if we manage to identify the right inhibitor, we may open the door to new therapeutic strategies that will be able to 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 healthy tissues, at least in adulthood.”
He concludes that if preclinical results confirm these findings, then clinical trials testing the theory may begin within a few years.
MNT recently reported on a study published in the International Journal of Cancer, which found that high levels of selenium – found in foods such as red meat and shellfish – may be linked to a reduced risk of colorectal cancer.