TGFB1 and cancer: SMAD-dependent TGF-β signaling induces JAG1 upregulation in the cancer cells and activates Notch 1 in osteoblasts within the niche which then secretes IL-6, stimulating the tumor growth and affecting osteoclast differentiation (Figure 5B) (Sethi et al., 2011; Wagley et al., 2020).