Fig. 2

The potential mechanism of tobacco-activated fibroblasts leading to carcinogenesis and cancer progression. Tobacco products can directly or indirectly stimulate fibroblasts to make a series of changes in their internal functions and signaling pathways. These changes will have a series of effects on the phenotype of peripheral epithelial cells (brown). For instance, growth factors released by tobacco-activated fibroblasts can promote the migration and invasion of peripheral cancer cells and induce epithelial-mesenchymal transformation. Tumor cells can use the high-energy metabolites produced by tobacco-activated fibroblasts for their own growth. Besides, one report showed that tobacco can promote metastasis of oral squamous cancer cells by suppressing miR-145 in fibroblasts