CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity.

Cell death and differentiation (2019-09-13)
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

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.

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Product Description

G 418 disulfate salt, powder, BioReagent, suitable for cell culture
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Cell Counting Kit - 8, for quantitation of viable cell number in proliferation and cytotoxicity assays
TNF- α Protein, Human Recombinant Animal Free, Tumor necrosis factor alpha (TNF-α), also known as cachectin & TNFSF1A, is the prototypic ligand of the TNF superfamily. Recombinant animal free human TNF-α is manufactured using all non-animal reagents.
Human Recombinant Animal Free