SMAD1 and neoplasm: Furthermore, Pan et al. indicated that overexpression of the CLOCK gene contributes to the progression of astrocytic brain tumors, among others, by exerting a promoting effect on the process of tumor angiogenesis and regulating the olfactomedin-like 3 (OLFML3) system—hypoxia-inducible factor 1-alpha (HIF1a)–transcriptional upregulation of periostin (POSTN)–TANK-binding kinase 1 (TBK1) [38]—and activating the canonical SMAD1/5/8 signaling pathway [39].