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. 2021 Apr 15;13(8):1890. doi: 10.3390/cancers13081890

Figure 1.

Figure 1

Role of laminin in oral cavity squamous cell carcinomas (OCSCC) progression. The figure illustrates the main mechanisms through which laminin is involved in OCSCC malignant phenotype acquisition. Up-regulation of the transcription factor Snail activates epithelial–mesenchymal transition (EMT), and consequently e-cadherin down-regulation, which enhances laminin 332 (LN-332) γ2 chain expression. Additionally, overexpression of claudin-1 leads to an increase in the expression of matrix metalloproteinase 2 (MMP-2) and membrane type 1 (MT1)—MMP, as well as to the cleavage rate of LN-332 (γ2) by these proteases, culminating in the migration and invasion of OCSCC. Also, EGFR gene amplification is associated with overexpression of γ2 chain (LAM γ2) that, in turn, hyperactivates EGFR/MAPK signaling pathway and, in a feedback circuit, increases LAM γ2expression. Moreover, the secreted LN-332 (γ2) is cleaved by MMP2 and MT1-MMP, generating the DIII fragment that can bind to EGFR, ending up in the activation of EGFR/MAPK pathway. Finally, the activation of EGFR/MAPK signaling pathway enhances proliferation and invasion rates of OCSCC cells. Dotted arrows: molecules secreted by OCSCC cells; solid arrows: activation of cellular events or intracellular signaling pathways; red solid arrow: overexpressed molecules; red boxes: activated signaling pathways; blue boxes: cleavage by MT1-MMP. BM = basement membrane.