The Rab25‐ ADAMTS5 axis as a previously undescribed mechanism for sensing tumor microenvironment complexity

The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a critical role in cancer progression. Focusing on ovarian cancer, Yuan et al. reveal an ECM‐dependent signaling axis where cancer‐associated fibroblasts (CAFs) enhance the invasiveness of cancer cells via Rab25‐driven upregulation of the protease ADAMTS5. This process is only triggered in the presence of native ECM. In turn, stimulated cancer cells favor CAF invasiveness through a mechanism that remains to be identified. These findings uncover a bidirectional crosstalk between cancer cells and CAFs and highlight the importance of context‐specific in vitro models to decipher ECM‐mediated tumor dynamics.