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AKIP1 promotes angiogenesis and tumor growth by upregulating CXC-chemokines in cervical cancer cells

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Abstract

Upregulation of A-kinase-interacting protein 1 (AKIP1) has been observed in breast and esophageal cancers, indicating that AKIP1 may be a potent oncogenic protein. However, the role of AKIP1 in cervical cancer still remains unknown. This study aimed to explore the role of AKIP1 in cervical cancer and to investigate the underlying mechanism of AKIP1 in tumor growth. Expression of AKIP1 in cervical cancer cells was determined by qRT-PCR and western blotting. Cell-Light EdU and colony formation assays were used to determine cell proliferation. CXCL1 and CXCL8 proteins were quantified by ELISA kits. Western blotting and qRT-PCR were used to examine the alterations in signaling-related proteins and mRNA, respectively. Endothelial cell tube formation assay was performed to evaluate the effect of AKIP1 on angiogenesis. A BALB/c nude mouse xenograft model was used to evaluate the role of AKIP1 in vivo. Cancer cell proliferation was inhibited and tumor growth and angiogenesis restrained in BALB/c nude mice by suppressing AKIP1 expression in cervical cancer cell lines. In addition, overexpression of AKIP1 in cervical cancer cells elevated the levels of CXCL1, CXCL2, and CXCL8. These three chemokines were not only involved in endothelial tube formation by binding to the endothelial receptor CXCR2, but also in cervical cancer cell proliferation and clone formation, which were induced by overexpression of AKIP1. Furthermore, we found that AKIP1-induced chemokine expression was decreased by an inhibitor of nuclear factor kappa-B kinase subunit β. These results show that AKIP1 is crucial in cervical cancer angiogenesis and growth by elevating the levels of the NF-κB-dependent chemokines CXCL1, CXCL2, and CXCL8.

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Acknowledgements

This study was supported by a Fund Project of the Changning District Science and Technology Commission (CNKW2015Y16).

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Authors and Affiliations

  1. Gynecology Department, Changning Maternity and Infant Health Hospital, 773#, Wuyi Rd., Shanghai, 200051, China

    Wenying Zhang, Qiongwei Wu, Chao Wang, Longtao Yang, Ping Liu & Chengbin Ma

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  1. Wenying Zhang
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  2. Qiongwei Wu
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Correspondence to Wenying Zhang.

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Zhang, W., Wu, Q., Wang, C. et al. AKIP1 promotes angiogenesis and tumor growth by upregulating CXC-chemokines in cervical cancer cells. Mol Cell Biochem 448, 311–320 (2018). https://doi.org/10.1007/s11010-018-3335-7

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  • DOI: https://doi.org/10.1007/s11010-018-3335-7

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