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

Oncogene volume 34, pages 384–393 (2015)Cite this article

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Abstract

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.

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Acknowledgements

This work was supported by the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2012), Natural Science Foundation of China (81325013, 81071780, 81030048, 91229101, U1201121, 81272196 and 81272198), the Science and Technology Department of Guangdong Province (S2011020002757 and S2012020010946) and Ministry of Education of China (20130171110085, 20120171110055).

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  1. C Lin, L Song and A Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangdong, China

    C Lin, L Song & X Lin

  2. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China

    C Lin, A Liu, H Gong & J Li

  3. Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China

    J Wu & M Li

  4. Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangdong, China

    J Wu, M Li & J Li

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Lin, C., Song, L., Liu, A. et al. Overexpression of AKIP1 promotes angiogenesis and lymphangiogenesis in human esophageal squamous cell carcinoma. Oncogene 34, 384–393 (2015). https://doi.org/10.1038/onc.2013.559

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