CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity

Ruo Yu Chen, Chia Jui Yen, Yao Wen Liu, Chun Guo Guo, Chieh Yu Weng, Chien Hsien Lai, Ju Ming Wang, Yih Jyh Lin, Liang Yi Hung

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

Centrosomal P4.1-associated protein (CPAP) is overexpressed in hepatocellular carcinoma (HCC) and positively correlated with recurrence and vascular invasion. Here, we found that CPAP plays an important role in HCC malignancies. Functional characterization indicated that CPAP overexpression increases tumor growth, angiogenesis, and metastasis ex vivo and in vivo. In addition, overexpressed CPAP contributes to sorafenib resistance. Mechanical investigation showed that the expression level of CPAP is positively correlated with activated STAT3 in HCC. CPAP acts as a transcriptional coactivator of STAT3 by directly binding with STAT3. Interrupting the interaction between CPAP and STAT3 attenuates STAT3-mediated tumor growth and angiogenesis. Overexpression of CPAP upregulates several STAT3 target genes such as IL-8 and CD44 that are involved in angiogenesis, and CPAP mRNA expression is positively correlated with the levels of both mRNAs in HCC. Knocked-down expression of CPAP impairs IL-6-mediated STAT3 activation, target gene expression, cell migration, and invasion abilities. IL-6/STAT3-mediated angiogenesis is significantly increased by CPAP overexpression and can be blocked by decreased expression of IL-8. Our findings not only shed light on the importance of CPAP in HCC malignancies, but also provide potential therapeutic strategies for inhibiting the angiogenesis pathway and treating metastatic HCC.

原文English
頁(從 - 到)1259-1273
頁數15
期刊Cell Death and Differentiation
27
發行號4
DOIs
出版狀態Published - 2020 四月 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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