CITED4 enhances the metastatic potential of lung adenocarcinoma.
CITED4 enhances the metastatic potential of lung adenocarcinoma.
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CITED4 增强肺腺癌的转移潜力
DOI：
10.1111/1759-7714.13831
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发表时间：
2021-05
期刊：
影响因子：
2.9
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Zhang L;Wang Y;Sha Y;Zhang B;Zhang R;Zhang H;Xu S;Wang H;Xu Y;Chen Y;Zhao X;Zhu J;Zhang Z;Wang C
CITED4属于CBP/p300 -与谷氨酸和天冬氨酸富尾相互作用的反激活因子家族，受多种细胞因子诱导，参与细胞因子诱导的增殖和分化。肺癌细胞中的CITED4是由HB‐EGF诱导的。然而，目前尚不清楚CITED4是否以及如何参与肺腺癌（ADC）的侵袭和转移。基于261例患者的队列分析了CITED4在肺腺癌中的表达及其与无病生存期（DFS）和总生存期的关系。通过功能丧失和功能获得实验验证了CITED4的作用。通过免疫组织化学、Western blotting和荧光素酶报告基因检测证实了CITED4和CLDN3之间的关系。CITED4‐CTNNB1‐CLDN3复合物的功能得到了充分的验证和描述。CITED4在ADC组织和细胞中的表达显著上调，是DFS的预测因子。下调CITED4可减弱细胞的增殖和侵袭，而过表达CITED4可增强这些作用。CITED4的过表达和敲低分别导致CLDN3的上调和下调。此外，在体内，CITED4下调可抑制CLDN3介导的ADC细胞转移。CITED4高表达，与CLDN3呈正相关。在机制上，CITED4与CTNNB1相互作用，协同作用增强CLDN3的转录。重要的是，CITED4通过CLDN3依赖性途径诱导ADC侵袭。CITED4决定了CLDN3的水平，进而影响肿瘤对产气荚膜梭菌肠毒素治疗的敏感性。CITED4‐CTNNB1‐CLDN3轴在ADC的侵袭和转移中发挥关键作用，为肺癌治疗提供了新的治疗靶点。CITED4在ADC组织和细胞中的表达显著上调。CITED4与CTNNB1相互作用，协同作用增强CLDN3的转录。CITED4‐CTNNB1‐CLDN3轴在ADC的侵袭和转移中发挥关键作用，为肺癌治疗提供了新的治疗靶点。
CITED4 belongs to the CBP/p300‐interacting transactivator with glutamic acid and aspartic acid‐rich tail (CITED) family which is induced by various cytokines and participates in cytokine‐induced proliferation and differentiation. CITED4 is induced by HB‐EGF in lung cancer cells. However, it is unclear whether and how CITED4 contributes to the invasion and metastasis of lung adenocarcinoma (ADC). CITED4 expression in lung adenocarcinoma and its association with disease‐free survival (DFS) and overall survival were analyzed based on a cohort of 261 patients. The roles of CITED4 were validated via loss‐of‐function and gain‐of‐function experiments. The relationship between CITED4 and CLDN3 was validated by immunohistochemistry, Western blotting, and luciferase reporter assays. The function of the CITED4‐CTNNB1‐CLDN3 complex was fully validated and described. CITED4 expression was significantly upregulated in ADC tissues and cells and a predictor for DFS. Downregulation of CITED4 attenuated the proliferation and invasion, whereas CITED4 overexpression enhanced these effects. Overexpression and knockdown of CITED4 resulted in the upregulation and downregulation of CLDN3, respectively. Moreover, CITED4 downregulation suppressed CLDN3‐mediated ADC cell metastasis in vivo. CITED4 was highly expressed and positively correlated with CLDN3. Mechanistically, CITED4 interacted with CTNNB1 and functioned synergistically to enhance CLDN3 transcription. Importantly, CITED4 induced ADC invasion via a CLDN3‐dependent pathway. CITED4 determined the level of CLDN3, which in turn affected the sensitivity of tumors to Clostridium perfringens enterotoxin treatment. The CITED4‐CTNNB1‐CLDN3 axis plays a key role in the invasion and metastasis of ADC and provides a novel therapeutic target for lung cancer treatment. CITED4 expression is significantly upregulated in ADC tissues and cells. CITED4 interacted with CTNNB1 and functioned synergistically to enhance CLDN3 transcription. The CITED4‐CTNNB1‐CLDN3 axis plays a key role in the invasion and metastasis of ADC and provides a novel therapeutic target for lung cancer treatment.
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影响因子：
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作者：
Zhang L;Wang Y;Zhang B;Zhang H;Zhou M;Wei M;Dong Q;Xu Y;Wang Z;Gao L;Qu Y;Shi B;Zhu J;Yin Y;Chen Y;Sun L;Zhang W;Xu S;Ying G;Wang C
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