Cancer overrides body clock to survive : The Tribune India

Join Whatsapp Channel

Cancer overrides body clock to survive

WASHINGTON: Cancer cells alter the body clock to boost tumour growth and survive conditions that would kill normal cells, a study has found.

Cancer overrides body clock to survive

Photo for representational purpose only. Thinkstock



WASHINGTON: Cancer cells alter the body clock to boost tumour growth and survive conditions that would kill normal cells, a study has found.

For tumours to grow and spread, cancer cells must make larger than normal amounts of nucleic acids and protein, so they can replicate themselves.

Yet in both normal and cancer cells that increase their synthesis of protein, a small percent of those proteins do not fold properly.

When that happens, the cell activates its unfolded protein response (UPR), which slows down the making of new proteins while the misfolded proteins are refolded.

Eventually, the buildup of misfolded proteins becomes toxic and leads to cell death.

However, cancer cells have learned to use the UPR to slow protein synthesis when needed, in order to handle the backlog of misfolded proteins. This helps them survive in conditions that would kill normal cells.

This pattern of adaptation is often seen in tumour cells, according to J Alan Diehl, from the Medical University of South Carolina (MUSC) in the US.

“What a tumour cell is doing is taking a pathway that’s already in the cell and using it to its advantage,” said Diehl.

Researchers used chemicals to activate the UPR in osteosarcoma cells. They found that, when activated, the UPR changes levels of an important protein called Bmal1, which is a transcription factor that rises and falls with cycles of light and dark.

As it does, it regulates the expression of major circadian rhythm genes. When cells were exposed to cycles of light and dark, Bmal1 levels peaked during dark hours.

When the UPR was chemically activated, Bmal1 stayed low during both light and dark phases, which caused a phase shift in the expression of circadian genes. When one of the main parts of the UPR machinery was absent in cells, the phase shift did not happen.

Researchers found that the UPR functions much like a “middleman” between light-dark cycles and the ability of cells to establish a circadian rhythm from those cycles.

Levels of the circadian protein Bmal1 continued to decrease, as the UPR was increasingly activated.

In rodents that had their light-dark cycles suddenly reversed, Bmal1 stopped rising and falling - a clear sign that their circadian rhythms were disrupted. Shifts in light exposure activated the UPR in those rodents’ cells.

Patients with breast, gastric or lung cancers survived longer 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 normal cells maintained it.

Conversely, high levels of Bmal1 overtook the UPR, thereby allowing protein synthesis to continue, which was toxic to tumour cells. In this way, Bmal1 directly encourages protein synthesis.

This is the first study showing that human cancer suppresses circadian rhythm by controlling protein synthesis through Bmal1.

“Physicians are beginning to think about timing delivery of therapies in such a way that, say, if we deliver a drug at a certain time of day, we’ll get better on-target effects on the cancer and less toxicity in the normal cells,” he said. PTI

Top News

Arvind Kejriwal to be produced before Delhi court today as 6-day ED custody ends

Excise policy case: Delhi court extends ED custody of Chief Minister Arvind Kejriwal till April 1

In his submissions, Kejriwal said, ‘I am named by 4 witnesse...

Delhi High Court dismisses PIL to remove Arvind Kejriwal from CM post after arrest

Delhi High Court dismisses PIL to remove Arvind Kejriwal from CM post after arrest

The bench refuses to comment on merits of the issue, saying ...

‘Unwarranted, unacceptable’: India on US remarks on Delhi CM Arvind Kejriwal’s arrest

‘Unwarranted, unacceptable’: India on US remarks on Delhi CM Arvind Kejriwal’s arrest

MEA spokesperson says India is proud of its independent and ...

Bullying Congress culture, no wonder being rejected: PM Modi, backs senior lawyers who flagged attempts to undermine public trust in judiciary

Bullying Congress culture, no wonder being rejected: PM Modi

Backs senior lawyers who flagged attempts to undermine publi...

Gujarat court sentences former IPS officer Sanjiv Bhatt to 20 years in jail in 1996 drug case

Gujarat court sentences former IPS officer Sanjiv Bhatt to 20 years in jail in 1996 drug case

Bhatt, who was sacked from the force in 2015, is already beh...


Cities

View All