This weeks lab journal club: nutrient restriction and PTEN-regulated growth, @elife

For our first journal club after the summer we picked an interesting paper from Hugo Stocker and co:

“Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic tissues”  published in elife.

The paper describes the interesting behaviour of pten mutant imaginal disc cells under different dietary protein (yeast) conditions. In rich food (high yeast) pten mutant cells overgrow compared to neighboring wild-type cells (which was already known). However, under nutrient-restricted conditions (low yeast) , the pten cells show massive overgrowth and a strong proliferative advantage versus their wildtype neighbours. This over-poliferation requires amino acid import and TOR signaling, but appears distinct from the cell competition and supercompetitor effects of factors such as Myc (e.g. see Moreno and Basler or De La Cova et al). Interestingly, under nutrient restrictive conditions the overgrowth of pten mutant cell clones in the eye disc triggered a systemic growth impairment  (other tissues such as the wing and fat body were smaller – although marginally so)

We liked this paper a lot. A few quick comments and thoughts that we tried to wrap our heads around:

– Do PTEN cells actively upregulate their AA or nutrient import under nutrient-deprivation conditions? It would be interesting (although difficult) to measure nutrient uptake in pten cells to see if they actively switch (upregulate) to ‘nutrient scavenging mode’ upon a switch to poor food, or whether their basal level of nutrient uptake is already high under rich food and just remains so when nutrients are scarce.

-what underlies the switch from hypertrophic growth (rich nutrients) to hyperplastic growth (poor nutrients) in pten cell clones? Is it simply due to increased cellular nutrient import? Or is there some ‘organ-level’ control of growth?

– What underlies the systemic growth impairment? Is it the case that the pten cells are very efficient at nutrient and growth factor ‘scavenging’ that growth in other tissues is reduced? The systemic growth impairment didn’t appear marked, so this ‘scavenging’ explanation may be right. Alternatively, is there some kind of signaling triggered by pten cells that induces a systemic endocrine response – similar to dilp8 release from damaged discs, which influences ecdysone release and whole body development (Colombani et al , Carelli et al)

– what about tsc1 mutant cells? they have overactive TOR signaling – would they phenocopy the pten cells with respect to growth in rich vs poor food? The editor/reviewer comments did suggest that the authors address this, and intriguingly, in their response, the authors indicated that the experiments were done but that the story was ‘rather complex’ – we look forward to hearing about this complex story.

Finally, we enjoyed reading the paper in elife, especially with the transparent reviewer comments and author responses. All journals should adopt this policy.

One thought on “This weeks lab journal club: nutrient restriction and PTEN-regulated growth, @elife

  1. Pingback: Lab Journal Club: Diet-induced insulin resistance and tumors in Drosophila | The Grewal Lab

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