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geneontology / go-ontology

Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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NTR: Methuosis #29270

Closed smoe closed 1 day ago

smoe commented 1 day ago
ValWood commented 1 day ago

Hi @smoe this appears to be a non-programmed cell death (i.e pathogenicity or cell killing caused by a toxic compound) and is therefore out of scope for GO (i.e. in the case of Rab5 and Rab7, blocks caused by changes in the activation states of these GTPases result in death)

smoe commented 1 day ago

Hi @ValWood,

Thank you for your swift reply and please apologize my initial set of references. I find the section on Methuosis in https://www.nature.com/articles/s12276-023-01078-x to be very convincing.

Since relevant for clinical environments, that is how I came across it and made me check if GO has it, I feel like we would miss something. So, yes, it is often induced, just like we may want to induce apopotosis, but in my understanding it is not something artificial per se.

Best, Steffen

remnants of my initial reply, all dwarfed by above Nature review.

Please have a look at https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.651982/full , which in my (admittedly biased) reading suggests that the physiological pinocytosis may be dysregulated and cause death.

And here https://pmc.ncbi.nlm.nih.gov/articles/PMC9267113/ it is described as programmed - even though my intuition initially stated something else. The problem I would have by not having the term in GO is that in clinical settings you want to be pointed to that term in enrichment analyses.

It is also something that I would expect to find in aging cells when transports go wrong.

ValWood commented 1 day ago

Hi @smoe, my hesitancy stems from the fact that we spent a lot of time cleaning up the types of cell death to remove cell death terms that are not programmed. These papers seem to describe a type of cytotoxicity in cancer cell lines and may be dependent on mutations in other key pathways in these cells. As such, it is not clear that they are a normal programmed process, but a consequence of the cancer cell line mutations. The review says Eventually, the vacuoles become sufficiently large to rupture the cell membrane, leading to cell death (Fig. 10 which implies a pathology rather than programmed death. Also it is often related to Ras overexpression (happens in many tumours). Methuosis has been observed in various cancer cell lines and has been proposed to be a potential therapeutic target for cancer treatment180,181. However, further research is required to fully understand the molecular mechanisms underlying methuosis and the potential of these mechanisms as targets for cancer therapy.

This isn't to say that it isn't an interesting phenotype of cancer cells and ageing, just that it is out of scope for GO because we only capture normal/programmed processes not pathology.

pgaudet commented 1 day ago

Thanks both for the input. Let's not create this term yet, base on what I read here it doesn't seem to be a normal process.