Washington, Dec 31 (PTI) Cancer cells alter the bodyclock to boost tumour growth and survive conditions that wouldkill normal cells, a study has found.
For tumours to grow and spread, cancer cells must makelarger than normal amounts of nucleic acids and protein, sothey can replicate themselves.
Yet in both normal and cancer cells that increase theirsynthesis of protein, a small percent of those proteins do notfold properly.
When that happens, the cell activates its unfoldedprotein response (UPR), which slows down the making of newproteins while the misfolded proteins are refolded.
Eventually, the buildup of misfolded proteins becomestoxic and leads to cell death.
However, cancer cells have learned to use the UPR to slowprotein synthesis when needed, in order to handle the backlogof misfolded proteins. This helps them survive in conditionsthat would kill normal cells.
This pattern of adaptation is often seen in tumour cells,according to J Alan Diehl, from the Medical University ofSouth Carolina (MUSC) in the US.
"What a tumour cell is doing is taking a pathway that'salready in the cell and using it to its advantage," saidDiehl.
Researchers used chemicals to activate the UPR inosteosarcoma cells. They found that, when activated, the UPRchanges levels of an important protein called Bmal1, which isa transcription factor that rises and falls with cycles oflight and dark.
As it does, it regulates the expression of majorcircadian rhythm genes. When cells were exposed to cycles oflight and dark, Bmal1 levels peaked during dark hours.
When the UPR was chemically activated, Bmal1 stayed lowduring both light and dark phases, which caused a phase shiftin the expression of circadian genes. When one of the mainparts of the UPR machinery was absent in cells, the phaseshift did not happen.
Researchers found that the UPR functions much like a"middleman" between light-dark cycles and the ability of cellsto establish a circadian rhythm from those cycles.
Levels of the circadian protein Bmal1 continued todecrease, as the UPR was increasingly activated.
In rodents that had their light-dark cycles suddenlyreversed, Bmal1 stopped rising and falling - a clear sign thattheir circadian rhythms were disrupted. Shifts in lightexposure activated the UPR in those rodents' cells.
Patients with breast, gastric or lung cancers survivedlonger when they had higher levels of Bmal1 protein. In myc-driven cancers, the UPR was causing the loss of Bmal1 protein,which caused the tumours to grow.
Myc-driven tumours lost circadian rhythm, whereas normalcells maintained it.
Conversely, high levels of Bmal1 overtook the UPR,thereby allowing protein synthesis to continue, which wastoxic to tumour cells. In this way, Bmal1 directly encouragesprotein synthesis.
This is the first study showing that human cancersuppresses circadian rhythm by controlling protein synthesisthrough Bmal1.
"Physicians are beginning to think about timing deliveryof therapies in such a way that, say, if we deliver a drug ata certain time of day, we'll get better on-target effects onthe cancer and less toxicity in the normal cells," he said.
PTI MHNMHN.
This is unedited, unformatted feed from the Press Trust of India wire.