SMAD3 and esophageal squamous cell carcinoma: As shown in Fig. 7E, it suggested that IGFBP-3 promoted esophageal squamous cell carcinoma (ESCC) cell cycle transition from G0/G1 to S phase via Smad3-P27/P21-cyclin E1/cyclin-dependent kinase (CDK2)–phosphorylated retinoblastoma protein (pRb) pathway signaling.