High stromal TGF-β signaling is associated with worse outcomes for patients with CRC.19 Here, we provide a potential mechanism underlying CAF heterogeneity, initiated by TGF-β and FOXL1, that polarizes fibroblasts toward Grem1highIslrlow CAFs or IslrhighGrem1low CAFs. This evidence concerns the gene FOXL1 and colorectal carcinoma.