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'Ancient' cellular discovery key to new cancer therapies

Metabolic system may explain tumour growth in humans

Date:
January 21, 2020
Source:
Flinders University
Summary:
Researchers have uncovered a metabolic system which could lead to new strategies for therapeutic cancer treatment. A team has found a link between a metabolic system in a yeast, and now mammals, which is critical for the regulation of cell growth and proliferation.
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Australian researchers have uncovered a metabolic system which could lead to new strategies for therapeutic cancer treatment.

A team at Flinders University led by Professor Janni Petersen and the St Vincent's Institute of Medical Research have found a link between a metabolic system in a yeast, and now mammals, which is critical for the regulation of cell growth and proliferation.

"What is fascinating about this yeast is that it became evolutionarily distinct about 350 million years ago, so you could argue the discovery, that we subsequently confirmed occurs in mammals, is at least as ancient as that," said Associate Professor Jonathon Oakhill, Head, Metabolic Signalling Laboratory at SVI in Melbourne.

This project, outlined in a new paper in Nature Metabolism, looked at two major signalling networks.

Often referred to as the body's fuel gauge; a protein called AMP-Kinase, or AMPK, regulates cellular energy, slowing cell growth down when they don't have enough nutrients or energy to divide.

The other, that of a protein complex called mTORC1/TORC1, which also regulates cell growth, increases cell proliferation when it senses high levels of nutrients such as amino acids, insulin or growth factors.

A hallmark of cancer cells is their ability to over-ride these sensing systems and maintain uncontrolled proliferation.

"We have known for about 15 years that AMPK can 'put the brakes on' mTORC1, preventing cell proliferation" says Associate Professor Oakhill. "However, it was at this point that we discovered a mechanism whereby mTORC1 can reciprocally also inhibit AMPK and keep it in a suppressed state.

Professor Petersen, from the Flinders Centre for Innovation in Cancer in Adelaide, South Australia says the experiments showed the yeast cells "became highly sensitive to nutrient shortages when we disrupted the ability of mTORC1 to inhibit AMPK."

"The cells also divided at a smaller size, indicating disruption of normal cell growth regulation," she says.

"We measured the growth rates of cancerous mammalian cells by starving them of amino acids and energy (by depriving them of glucose) to mimic conditions found in a tumour.

"Surprisingly, we found that these combined stresses actually increased growth rates, which we determined was due to the cells entering a rogue 'survival' mode.

"When in this mode, they feed upon themselves so that even in the absence of appropriate nutrients the cells continue to grow.

"Importantly, this transition to survival mode was lost when we again removed the ability of mTORC1 to inhibit AMPK."

These findings provide a new opportunity for cancer treatment strategies aimed at suppressing cell proliferation in the nutrient-poor tumour microenvironment, the research concludes.


Story Source:

Materials provided by Flinders University. Note: Content may be edited for style and length.


Journal Reference:

  1. Naomi X. Y. Ling, Adrian Kaczmarek, Ashfaqul Hoque, Elizabeth Davie, Kevin R. W. Ngoei, Kaitlin R. Morrison, William J. Smiles, Gabriella M. Forte, Tingting Wang, Shervi Lie, Toby A. Dite, Christopher G. Langendorf, John W. Scott, Jonathan S. Oakhill, Janni Petersen. mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress. Nature Metabolism, 2020; DOI: 10.1038/s42255-019-0157-1

Cite This Page:

Flinders University. "'Ancient' cellular discovery key to new cancer therapies." ScienceDaily. ScienceDaily, 21 January 2020. <www.sciencedaily.com/releases/2020/01/200121112926.htm>.
Flinders University. (2020, January 21). 'Ancient' cellular discovery key to new cancer therapies. ScienceDaily. Retrieved April 22, 2024 from www.sciencedaily.com/releases/2020/01/200121112926.htm
Flinders University. "'Ancient' cellular discovery key to new cancer therapies." ScienceDaily. www.sciencedaily.com/releases/2020/01/200121112926.htm (accessed April 22, 2024).

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