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CUEDC1 inhibits epithelial-mesenchymal transition via the T?RI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer.


ABSTRACT: Lung cancer remains the most lethal cancer worldwide because of its high metastasis potential. Epithelial-mesenchymal transition (EMT) is known as the first step of the metastasis cascade, but the potential regulatory mechanisms of EMT have not been clearly established. In this study, we first found that low CUEDC1 expression correlated with lymph node metastasis in non-small cell lung cancer (NSCLC) patients using immunohistochemistry (IHC). CUEDC1 knockdown promoted the metastasis of NSCLC cells and EMT process and activated T?RI/Smad signaling pathway. Overexpression of CUEDC1 decreased the metastatic potential of lung cancer cells and inhibited the EMT process and inactivated T?RI/Smad signaling pathway. Immunoprecipitation (IP) assays showed that Smurf2 is a novel CUEDC1-interacting protein. Furthermore, CUEDC1 could regulate Smurf2 expression through the degradation of Smurf2. Overexpression of Smurf2 abolished CUEDC1 knockdown induced-EMT and the activation of T?RI/Smad signaling pathway, while siRNA Smurf2 reversed CUEDC1 overexpression-mediated regulation of EMT and T?RI/Smad signaling pathway. Additionally, CUEDC1 inhibited proliferation and promoted apoptosis of NSCLC cells. In vivo, CUEDC1-knockdown cells promoted metastasis and tumor growth compared with control cells. In conclusion, our findings indicate that the crucial role of CUEDC1 in NSCLC progression and provide support for its clinical investigation for therapeutic approaches.

SUBMITTER: Cui Y 

PROVIDER: S-EPMC7655170 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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CUEDC1 inhibits epithelial-mesenchymal transition via the TβRI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer.

Cui Yue Y   Song Yang Y   Yan Shi S   Cao Mengru M   Huang Jian J   Jia Dexin D   Liu Yuechao Y   Zhang Shuai S   Fan Weina W   Cai Li L   Li Chunhong C   Xing Ying Y  

Aging 20201025 20


Lung cancer remains the most lethal cancer worldwide because of its high metastasis potential. Epithelial-mesenchymal transition (EMT) is known as the first step of the metastasis cascade, but the potential regulatory mechanisms of EMT have not been clearly established. In this study, we first found that low CUEDC1 expression correlated with lymph node metastasis in non-small cell lung cancer (NSCLC) patients using immunohistochemistry (IHC). CUEDC1 knockdown promoted the metastasis of NSCLC cel  ...[more]

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