IGF1 and breast cancer: Furthermore, in a recent study using a murine model of breast cancer, CSCs have shown to produce the Hedgehog (Hh) ligand Sonic Hedgehog (SHH), activating the Hh signaling pathway in CAFs, which leads to increased CAF proliferation and ECM deposition and enhances the production of other factors such as ACTIVIN A, insulin-like growth factor 1 (IGF-1) and leukemia inhibitory factor (LIF), which result in CSC growth and self-renewal [70], in a feedback communication between CAFs and CSCs.