CCND1 and neoplasm: Of paramount significance, Cai et al. while affirming the previously mentioned outcomes regarding ESCC cell proliferation and cycle arrest, additionally demonstrated that the in vivo anti-tumor effects of metformin in an ESCC xenograft model are associated with the upregulation of AMPK, p53, p21CIP1, and p27KIP1, along with the downregulation of cyclin D1 [52].