A-kinase-interacting Protein 1 Expression Research Articles

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

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.

Overexpression of AKIP1 promotes angiogenesis and lymphangiogenesis in human esophageal squamous cell carcinoma

A-kinase-interacting protein 1 (AKIP1) is found to be overexpressed in breast and prostate cancers, suggesting that AKIP1 might act as a potent oncogenic protein. However, the clinical significance and biological role of AKIP1 in cancer progression remain largely unknown. Herein, we report that AKIP1 is markedly overexpressed in esophageal squamous cell carcinoma (ESCC) cell lines and clinical ESCC samples. AKIP1 expression significantly correlates with ESCC progression and patients' shorter survival time. Furthermore, we find that overexpressing AKIP1 induces, whereas silencing AKIP1 reduces, ESCC angiogenesis and lymphangiogenesis both in vitro and in vivo. Moreover, we demonstrate that AKIP1 transcriptionally upregulates vascular endothelial growth factor-C (VEGF-C) via interaction with its promoter through cooperation with multiple transcriptional factors, including SP1, AP2 and nuclear factor-κB (NF-κB). Importantly, significant correlation between levels of AKIP1 and VEGF-C is observed in a cohort of human ESCC, as well as in non-small cell lung cancer, hepatocellular carcinoma and ovarian cancer. Hence, these findings indicate an important role for AKIP1 in ESCC angiogenesis and lymphangiogenesis, and uncover a novel mechanism for the upregulation of VEGF-C in cancers.

A-kinase-interacting Protein 1 (AKIP1) Acts as a Molecular Determinant of PKA in NF-κB Signaling

A-kinase-interacting Protein 1 (AKIP1) Acts as a Molecular Determinant of PKA in NF-κB Signaling