Many thanks to all collaborators (including @cperezgonzalez.bsky.social, @vignjeviclab.bsky.social @vanrheenenlab.bsky.social, @hugosnippert.bsky.social) and the Dutch Cancer Foundation for making this work possible!

In future work we hope to unravel how TRPV4 and integrins cooperate to control YAP signaling in CRC cells, and how mechanical forces intersect with other cues controlling CRC cell plasticity

Chemical activation of mechanosensitive calcium channels is sufficient to trigger the emergence of fetal-like cells, and screening channels expressed in CRCs points to TRPV4 as the key channel. Blocking both integrin signaling and TRPV4 fully prevents Collagen I–induced reprogramming

CRC cells pulling on Collagen I show increased calcium fluctuations, visualized with the calcium reporter K-GECO1

CRC reprogramming by mechanical interactions with Collagen I involves the usual suspects: induction of YAP-mediated transcription via integrins. Interestingly, we find that for this integrins team up with other mechanosensors: mechanosensitive calcium channels

…which requires CRC cells to mechanically pull on the Collagen I network (e.g., being disrupted when plating CRC cells on collagen I-coated substrates of low stiffness).

Using CRC organoid models we found that interactions with Collagen I, a main component of the stroma, can trigger this reprogramming…

Consistent with previous work (including from @vanrheenenlab.bsky.social), spatial transcriptomic analysis of colorectal cancer (CRC) shows that cells invading the stroma lose Lgr5-stem cell signatures. We show that these cells adopt a fetal-like transcriptional program

We finally made it over here ! And excited to share our new paper on mechanical forces regulating stem cell plasticity in colorectal cancer, involving force transduction via mechanosensitive calcium channels! www.cell.com/cell-reports...

1/ 🎉Excited to share our new preprint @vignjeviclab.bsky.social @davidbrueckner.bsky.social : "Self-organization of tumor heterogeneity and plasticity" biorxiv.org/content/10.1... Tumor heterogeneity and plasticity drive metastasis and relapse. How is tumor patterning coordinated? A thread👇