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Autophagy Predicts Which Cancer Cells Live or Die When Faced with Anti-Cancer Drugs

As medicine and biotechnology are developing rapidly, it appears that the day people conquer cancers is approaching. Yet, various anti-cancer drugs spring up usually on the basis of theoretical possibility, or are only effective for mice – some cancer cells always survive the drug attacks.

How do these cancer cells combat anti-cancer drugs? Recently, a new study published in Nature Cell Biology by Andrew Thorburn, PhD, deputy director of the Colorado University Cancer Center, proposed that cancer cells’ anti-drug ability might come from a process, known as autophagy, where cells are able to cleanse themselves.

Past studies demonstrate that autophagy can promote cell survival –under conditions of shortage or stress, cells break down non-necessary components to provide energy or use such strategy to prevent cellular damage by degrading and recycling potentially damaging proteins. However, autophagy is not always a benign process and it seems more like an unrestrained gambling when there is no way out for cells. Currently, people know little about the specific process of autophagy and associated influencing factors.

Thorburn speculated that when cancer cells combat drugs, cells’ life and death are affected by autophagy. He firstly used flow cytometry technique to separate HELA cells with high-autophagy and low-autophagy cell populations and then treated them with chemicals TRAIL and Fas ligand, which activate cell’s death receptors. The results showed that cells with high autophagy were more sensitive to treatment with Fas ligand, whereas cells with low autophagy were more sensitive to TRAIL.

Based on this interesting results, Thorburn further conducted specific signal path study on the autophagy under these two situations and found that after TRAIL treatment, high-autophagy cells degrade cappase-8, an enzyme that promotes apoptosis, and hence prevents cell death; whereas upon Fas ligand treatment, high-autophagy cells degrade FAP-1 protein instead of cappase-8, making cells more susceptible to Fas ligand and leading to a higher mortality.

 “When facing with anti-cancer drugs, autophagy of cancer cells will decide their final destiny,” said Thorburn. Moreover, added Thorburn, the cancer cells used in this study had small difference in autophagy, while in real tumors, their autophagy level may be very different and so do their responses, making autophagy play a significant role in deciding which cells to live or die.

Cancer cell autophagy

During autophagy, cancer cells eat parts of themselves to get through conditions of stress and shortage. *Image source: coloradocancerblogs.org

Thorburn’s study reminds people that we can’t ignore the influence of cancer cell autophagy. Next, they will investigate potential anti-cancer drugs using similar approach.

In current cancer treatment, researchers tend to believe that autophagy can promote survival rate of cells and thus suppress the process without exception and keep cancer cells in a nearly ideal status. Perhaps, in future research, scientists should selectively control autophagy that is sensitive to some drugs and make one step of cancer research forward.

Source: EurekAlert!

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