CCN2 and cancer: When HSCs are activated, they secrete growth factors such as transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF) into the TME, resulting in the activation of cancer-stroma leading to enhanced cancer cell proliferation, excessive ECM synthesis, EMT and invasion, as well as drug resistance [21].