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

…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