Scientists just found cancer cells’ hidden power source

[Mij]

Defensive mechanism's discovery could help pin cancer down before it spreads

When cancer cells are physically squeezed, they mount an instant, high-energy defense by rushing mitochondria to the cell nucleus, unleashing a surge of ATP that fuels DNA repair and survival. This newly discovered mechanism, visualized in real time with advanced microscopy, shows mitochondria acting like emergency first responders rather than static power plants. The structures, called NAMs, were also identified in patient tumor biopsies, suggesting real-world relevance to cancer’s spread.

"Wherever cells are under pressure, a nuclear energy boost is likely safeguarding the integrity of the genome," concludes Dr. Sdelci. "It's a completely new layer of regulation in cell biology, marking a fundamental shift in our understanding of how cells survive intense periods of physical stress."

 

[Creekside]

Hmmm, not convinced this is a major discovery about cancer. Most cancer cells aren't physically squeezed, so this wouldn't play a role in typical cancer. It might be an important discovery for other aspects of biology.

 

[boolybooly]

What bugs me about the treatment of cancer in the media is the way it is often regarded as if an entity with its own agenda rather than pathology of an organism.

If that was the case then it would imply that cancer was due to a reproductory gambit by another organism like a virus.

I have not kept up with modern research on this and wonder to what extent available evidence suggests cancer is engineered by a virus and therefore capable of evolution by natural selection and to what extent it is considered instead incidental pathology of complex developmental systems in host tissues in which case attribution of intent is misconceived and observed behaviours have to be interpreted as pathology of extant host systems.

 

[Jaybee00]

It’s a university press release.

 

[jnmaciuch]

What bugs me about the treatment of cancer in the media is the way it is often regarded as if an entity with its own agenda rather than pathology of an organism.

If that was the case then it would imply that cancer was due to a reproductory gambit by another organism like a virus.

I have not kept up with modern research on this and wonder to what extent available evidence suggests cancer is engineered by a virus and therefore capable of evolution by natural selection and to what extent it is considered instead incidental pathology of complex developmental systems in host tissues in which case attribution of intent is misconceived and observed behaviours have to be interpreted as pathology of extant host systems.

I don’t think it’s a wrong way to talk about cancer cells, per se, because fundamentally evolution acts on a whole set of genetic material that gets replicated and passed down as a unit. When you have a set of cells that become genetically distinct from surrounding cells due to an oncogenic mutation and start to bypass systemic regulatory mechanisms of cell division, these cells are now being acted upon by evolutionary mechanisms as a unicellar unit rather than part of a multicellular one that undergoes natural selection through sexual reproduction.

Populations of cancer cells evolve genetically over time and are absolutely subject to the rules of natural selection. Things like metastasis, for example, are often driven by positive selection of mutations that facilitate invasion of blood vessels.

It’s ultimately a semantic argument, since nothing has intent or an agenda in the process of evolution. But to the extent that you can project “intent” from a human perspective, cancer cells do have a different “agenda” than the rest of the non-cancerous cells in an organism—the dynamics become pretty much the same as a viral population undergoing intrahost evolution. It really is a reproductory gambit for cancer cells [edit: to the extent that anything can be called that when we humans use imprecise language to talk of evolution]

 

[Jonathan Edwards]

What bugs me about the treatment of cancer in the media is the way it is often regarded as if an entity with its own agenda rather than pathology of an organism.

If that was the case then it would imply that cancer was due to a reproductory gambit by another organism like a virus.

Yes, I agree with jnmaciuch, there is evolution going on in a cancer, with mutation and selection within a clone and then subclones. It is a dynamic entity in the sense that it has its own specific set of rules. There is no need to invoke a virus or a 'gambit'.

Some cancers are virus initiated but I think there is very little evidence for the virus depending on the malignant transformation for infecting other individuals.

I think the idea of gambits or strategies in evolution is best avoided, since there is no forward planning implied in Darwin. Of all the species that have lived on the planet, 99% failed to survive. Of all the multicellular organisms it is more like 99.99999%. failed to survive. The extraordinarily long wing feathers of the male argus pheasant and its bower-making, which in most cases never attracts a mate, is not so much a strategy as a group of cells stuck in a trajectory going nowhere!

 

[jnmaciuch]

Hmmm, not convinced this is a major discovery about cancer. Most cancer cells aren't physically squeezed, so this wouldn't play a role in typical cancer. It might be an important discovery for other aspects of biology.

Cancer cells do get squeezed inside a tumor. This mechanism could very likely play a role in the growth of a tumor, enabling a small tumor to continue actively replicating and possibly accumulate more deleterious mutations

 

[SNT Gatchaman]

Mitochondria-derived nuclear ATP surge protects against confinement-induced proliferation defects

Spoiler: Authors

Ghose, Ritobrata; Pezzano, Fabio; Badia, Rémi; Kourtis, Savvas; Sheraj, Ilir; Das, Shubhamay; Gañez Zapater, Antoni; Ghose, Upamanyu; Musa-Afaneh, Sara; Espinar, Lorena; Coll-Manzano, Albert; Parapatics, Katja; Ivanova, Saška; Sànchez-Fernàndez-de-Landa, Paula; Radivojevikj, Dragana; Venturini, Valeria; Wieser, Stefan; Zorzano, Antonio; Müller, André C; Ruprecht, Verena; Sdelci, Sara

The physical tissue microenvironment regulates cell state and behaviour. How mechanical confinement rewires the subcellular localisation of organelles and affects cellular metabolism is largely unknown.

In this study, proteomics analysis revealed that cellular confinement induced a strong enrichment of mitochondrial proteins in the nuclear fraction. Quantitative live cell microscopy confirmed that mechanical cell confinement leads to a rapid re-localisation of mitochondria to the nuclear periphery in vitro, reflecting a physiologically relevant phenomenon in patient-derived tumours. This nucleus-mitochondria proximity is mediated by an endoplasmic reticulum-based net that entraps the mitochondria in an actin-dependent manner.

Functionally, the nucleus-mitochondria proximity results in a nuclear ATP surge, which can be regulated by the genetic and pharmacological modulation of mitochondrial ATP production or via alterations of the actin cytoskeleton. The confinement-induced nuclear ATP surge has physiologically significant long-term effects on cell fitness, driven by changes in chromatin state, enhanced DNA damage repair, and cell cycle progression during mechanical cell deformation.

Together, our data describe a confinement-induced metabolic adaptation that is required to enable prompt DNA damage repair and cell proliferation under mechanical confinement stress by facilitating chromatin state transitions.

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