Abstract
Cell differentiation, driven by switching from stem cell- into differentiation-program, generates functionally and morphologically distinct cell types, accompanied with decelerated cell proliferation. In this study, we reported that a group of lung cancer cells generated cancer plasticity by switching between SOX2- and SOX9-mediated program, thus forming differential proliferation and invasion abilities. We found that SOX2 bound EPCAM promoter to induce EpCAM-p21Cip1-cyclin A2 signaling, hence encouraging cell proliferation as well as barrier properties. In contrast, SOX9 bound SLUG promoter to encourage SLUG-mediated cancer cell invasion with a spindle-like phenotype. Pharmacological inhibition of HDACs elevated SOX9-positive population from SOX2-postive cells whereas ectopic expression of SOX2 inhibited SOX9 with increased H3K9me2 levels on SOX9 promoter. Furthermore, SOX2 and SOX9 expression were negatively and positively correlated with lung tumor grades, respectively. Our findings support the involvement of epigenetic regulation in the SOX2- and SOX9-mediated cancer plasticity, providing critical insights for cancer progression.