Cancer cells' survival strategy defeated with new approach
Wednesday 14/March/2018 - 01:07 PM
Some cancers put up a fight against regular treatments such as chemotherapy or radiotherapy due to their various "strategies" for survival. But by manipulating cellular processes، scientists have now found a way of bypassing one of cancer's self-preservation mechanisms. Autophagy — a term meaning "self-devouring" in Greek — is، normally، cells' way of staying orderly and functional.
This is due to the fact that when autophagy is triggered، cells break down the elements that aren't useful any longer and "recycle" material for reuse.
This process has been shown to have complex implications for cancer cells; sometimes it helps to destroy them، but at other times it helps them to thrive.
One way in which cancer cells use autophagy "in their own interest" is to evade apoptosis، or cell death.
Apoptosis and autophagy both rely on similar mechanisms to break down cellular material that is no longer helpful. But while apoptosis takes this disassembly all the way، eventually causing the cell to die، in autophagy، death is postponed by recycling some of the cellular material.
In many cases، researchers have discovered that chemotherapy and radiotherapy can increase the presence of autophagy in cancer cells، which actually allows them to enter a "hiatus" mode that helps them to evade cell death and resume their activity later.
While researchers have studied the importance of autophagy inhibitors in promoting apoptosis، the underlying mechanisms that allow cell death to occur when this recycling process is inhibited have remained unclear.
Now، researchers from the University of Colorado Cancer Center in Aurora have begun to uncover some of these mechanisms، which has also allowed them to develop a fresh strategy to bypass tumor cells' autophagy and trigger their death more efficiently. Medics today said.
The results of the study — which was led by Andrew Thorburn — have now been published in the journal Developmental Cell.
Autophagy as 'suspended animation' In the new study، the researchers explain that the so-far mysterious link between autophagy and apoptosis is transcription factor FOXO3a، which is a protein that carries with it "instructions" as to what should take place at cellular level.
"The problem،" says Thorburn، "is this: many anti-cancer treatments push cancer cells to the brink of death. But the cells use autophagy to go into a kind of suspended animation، pausing but not dying."
It turns out that FOXO3a plays a key role in the cellular homeostasis related to autophagy — that is، it helps to regulate that process. Interestingly، though، autophagy also helps to regulate the levels of this transcription factor.
In other words، when the presence of autophagy is increased، FOXO3a levels go down، and when autophagy is downregulated، more FOXO3a is produced، thereby boosting the cellular recycling process. This means that autophagy remains at constant levels، sometimes despite the action of chemotherapy drugs.