Cancer manipulates biologically useful systems to its selfish advantage (dual role of autophagy)
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Prolonged fasting stimulates autophagy, an intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy is thought to be part of a coordinated biological process that is important for exposing cancer cells to the immune system, ultimately leading to their weakening and death. However, the relationship between autophagy and cancer is complicated. In a desperate effort to proliferate, cancer cells may exploit autophagy to obtain the cellular components they require for rapid growth. Autophagy may prevent the survival of pre-malignant cells, but the process can also be hijacked as a malignant adaptation by cancer cells to scavenge resources. In this clip, Dr. Valter Longo discusses how autophagy may function in both normal and cancer cells.
Rhonda: Do you think there's some, sort of, like, different stage of cancer where this is, you know, autophagy becomes more important like later in cancer, when they'd actually that's when the metastasis occurs? Or what do you think of that whole field of, you know, autophagy also playing a role in cancer?
Valter: I think the autophagy, and I think this was in the paper that was published together with ours by Guido Kroemer, and he showed...and Frank Madeo has also being doing work on that. But Guido was showing that autophagy was very important during the starvation, or using starvation mimicking drugs in causing the exposure of cancer cells to the immune system, right? So, which probably means that the autophagy is really part of this weakening and maybe death of the cancer cells. So, autophagy turns from something good, in a normal cell, that it does in a very coordinated way into something bad in a cancer cell, probably because it might break down components that are needed.
I mean, I don't know, but certainly, you know, autophagy seems to be, you know, at least for this purpose, it seems to be very important, and probably part of the desperate attempt of cancer cells to get what they need from somewhere. And that's what we see that, in general, we've seen that for almost everything else. I mean, even independent of autophagy, the desperation seems to be key. Meaning that, for example, they try to increase translation, to get more proteins, right? Instead of shutting down like a normal cell would, they go and try to do things that they seem to be desperate. And, of course, you can't do that, or you can do it only for so long, and that's probably why they die.
Rhonda: Yeah. I mean, I know it was something that kinda was confusing to me at first, and then I thought about it for, you know, a little more in-depth. And I thought, well, fasting itself is doing so much more than just autophagy as well, so it's not like that's the only mechanism that's occurring, biological mechanism that's changing with fasting. But I just thought it was, kind of, interesting how it seems to be theirs, sort of, this opposite end of the spectrum, you know, effects in terms of cancer.
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.
Cancer that has spread from the part of the body where it started to other parts of the body. When cancer cells break away from a tumor, they can travel to other areas of the body through the bloodstream or the lymph system.
A type of intermittent fasting that exceeds 48 hours. During prolonged periods of fasting, liver glycogen stores are fully depleted. To fuel the brain, the body relies on gluconeogenesis – a metabolic process that produces glucose from ketones, glycerol, and amino acids – to generate approximately 80 grams per day of glucose [1]. Depending on body weight and composition, humans can survive 30 or more days without any food. Prolonged fasting is commonly used in the clinical setting.
[1] Longo, Valter D., and Mark P. Mattson. "Fasting: molecular mechanisms and clinical applications." Cell metabolism 19.2 (2014): 181-192.
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