Notum Promotes Proliferation and Migration of Oral Squamous Cell Carcinoma Via Shh/p-GSK3β/β-Catenin Pathway

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, accounting for more than 90% of oral and maxillofacial malignancies. Therefore, it is of great importance to explore the key factors regulating OSCC. Notum belongs to the α/β hydrolase family and is a deacylated extracellular protein that regulates Wnt and other signaling pathways. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma and targeting Notum can regulate the occurrence of cancer. However, the relationship between Notum and OSCC is currently unclear. This study aims to explore the role of Notum in regulating OSCC and its specific mechanism. Methods: Nine OSCC tissue sections were selected for hematoxylin and eosin staining and immunohistochemistry for PCNA and Notum. Bioinformatics analysis was used to explore the correlation between OSCC and Notum expression. CCK8, Western blot, RT-PCR, scratch experiment, transwell, clone formation, flow cytometry, cellular immunofluorescence and in vivo nude mouse tumor formation methods were applied to OSCC cells treated with Notum human recombinant protein, a Notum overexpression plasmid, and a Notum small interfering RNA to explore the mechanism of Notum in regulating OSCC. Results: The results of immunohistochemistry and bioinformatics analysis showed that Notum was highly expressed in OSCC tissues. Notum human recombinant protein promoted the proliferation and migration of Cal-27 and SCC-15 cells; overexpression of Notum promoted the proliferation and migration of Cal-27 and SCC-15 cells; si-Notum can significantly inhibit proliferation and migration of Cal-27 and SCC-15 cells and promote their apoptosis. Western blot and RT-PCR results showed that si-Notum can inhibit the Hedgehog signaling pathway. In addition, Notum human recombinant protein can increase the phosphorylation level of GSK3β and promote the expression of β-catenin, thereby further regulating the biological behavior of OSCC.Conclusions: Notum regulates the proliferation and migration of OSCC through Shh/p-GSK3β/β-catenin signaling pathway. Notum maybe an effective targets for the treatment of OSCC.