Thank you so much Kirsteen 😊

Vassili, thank you very much for your kind words 😊

Martha, thank you for your support and kind words 😊

@cassiejclarke.bsky.social, thank you very much for the wonderful supervision 😊

Thank you very much Paulina 😄

Thank you very much Guillaume 😊

10/ Massive thanks to @cassiejclarke.bsky.social and Jim for the wonderful supervision and @cancerresearchuk.org for the funding.
@uofglasgow.bsky.social @uofgcancersciences.bsky.social

Hope you enjoy reading!!

9/ Grateful to everyone that made this possible, especially members of the Norman lab for their great contribution @vanecitav.bsky.social @ruhi-d.bsky.social and members of the @ivaskalab.bsky.social for the unwavering support.

8/ Profoundly thankful to D. Sumpton, E. Shokry, S.Tardito for their metabolic expertise, K. Blyth and @louisemitchell21.bsky.social for their invaluable insights into the in vivo models. All the core facilities and services @cruk-si.bsky.social for the amazing work.

7/ Interestingly, disruption of Rab27s opposes EV release from primary tumour cells, but not from micrometastatic cells. Lastly, we show that the switch to nSM2-dependent EV release enables micrometastatic cells to influence #ECM deposition by fibroblasts to foster an invasive #microenvironment.

6/ Following the observation that ceramides are enriched in micrometastatic cells, we disrupted the expression of n. sphingomyelinases known to influence EV release. We found that reduction of nSM2, but not nSM1, significantly reduces ceramide levels and EV release from micrometastatic cells.

5/ In addition to their altered polar metabolism, we uncover that micrometastatic cells display elevated levels of distinct #ceramide species, which are also enriched in their EVs and are present at significantly higher levels in the plasma of metastatic breast cancer patients.

4/ Given the importance of #EVs in metastatic niche priming, we sought to examine the relationship of EV release from micrometastatic cells to their altered metabolism. We found that decreased ability to synthesise glutathione is associated with increased EV release.

3/We further demonstrate that proline and glutathione pathways compete for glutamine-derived carbons in micrometastatic cells. The adoption of this metabolic profile, in which proline and glutathione levels are, respectively, elevated and suppressed, is a feature unique to micrometastatic cells.

2/ We generated isogenic cells from primary mammary tumours and their corresponding lung micrometastases. We show that micrometastatic cells increase proline production and circulating proline is significantly elevated in mice and patients with metastatic disease.

10/ Massive thanks to @cassiejclarke.bsky.social and Jim for the wonderful supervision and @cancerresearchuk.org for the funding.
@uofglasgow.bsky.social @uofgcancersciences.bsky.social

Hope you enjoy reading!!