In another CRC model established using freshly isolated carcinoma cells and the paired CAFs, CAFs up-regulated the expression of TGF-β2 and IL-6, which activated the expression of GLI family zinc finger (GLI)-2 in the sonic hedgehog (SHH) pathway, resulting in the transdifferentiation of cancer cells into CSCs and chemotherapy resistance (65). This evidence concerns the gene IL6 and cancer.