Title: LAMC2 promotes oral squamous cell carcinoma growth by activating the p-ERK/c-Myc signaling pathway

Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck carcinoma. Limited therapies are available for OSCC due to lack of molecular therapeutic targets. Methods: Bioinformatics analysis, in vitro experiments and animal model studies were performed to elucidate the crucial role and clinical significance of LAMC2 in the progression of OSCC. And we examined the mRNA and protein levels of LAMC2 in human OSCC tissue to explore the biological significance of LAMC2. Results: We identified Laminin γ2 (LAMC2), a crucial oncoprotein, were upregulated in human OSCC samples in TCGA datasets. The upregulated LAMC2 was related to poorer survival rates, increased the risk of OSCC-specific mortality, and there were significant differences in survival between the LAMC2 high and low expression groups. We also validated that the mRNA and protein expression of LAMC2 were upregulated in human OSCC samples compared with the para-tumor tissues. LAMC2 overexpression significantly enhanced cell proliferation, invasion and migration. Mechanistically, overexpression of LAMC2 could increase the expression levels of p-ERK and c-Myc, while knockdown of LAMC2 resulted in the opposite effect. Moreover, the ERK inhibitor decreased ERK phosphorylation and reversed the OSCC phenotype induced by LAMC2 overexpression. Conclusion: LAMC2 enhances the cell proliferation, invasion and migration of OSCC cells via the p-ERK/c-Myc axis, suggesting the crucial role of LAMC2 in the progression of OSCC and small molecule inhibitors targeting LAMC2 might be an effective treatment for OSCC patients.