DLL4 and colorectal cancer: For instance, DLL4 was shown to enhance stemness through the activation of the NOTCH3 receptor, resulting in the overexpression of the stemness marker MUSASHI-1 (Okano et al., 2005; Bley et al., 2021) and inhibition of the NUMB protein (Pastò et al., 2014; Choi et al., 2021) in both colorectal cancer cell lines and primary cultures of colorectal cancer metastases (Figure 3).