Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently uncl...Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma(OSCC)-derived small extracellular vesicles(s EVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition(EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in s EV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, mi Rlet-7c in OSCC-derived s EVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived s EVs promote the precancerous transformation of normal epithelial cells, in which the mi R-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through s EVs, which provides new insight into the progression of OSCC.展开更多
基金supported by the National Natural Science Foundation of China(Grant no.81972547 to Zhengjun Shang)。
文摘Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma(OSCC)-derived small extracellular vesicles(s EVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition(EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in s EV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, mi Rlet-7c in OSCC-derived s EVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived s EVs promote the precancerous transformation of normal epithelial cells, in which the mi R-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through s EVs, which provides new insight into the progression of OSCC.
