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p55PIK-PI3K stimulates angiogenesis in colorectal cancer cell by activating NF-κB pathway

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Abstract

Vascular growth factor (VEGF) is an important mediator of angiogenesis. PI3K plays essential roles in angiogenesis; however, the mechanisms and specific functions of individual isoforms of PI3K members in tumor angiogenesis regulation are still not fully understood. In this study, we evaluate the role of p55PIK, a PI3K regulatory subunit encoded by PIK3R3 gene, in tumor angiogenesis. We reported that overexpression of p55PIK in cancer cells up-regulated HIF-1α expression and increased VEGF expression. Furthermore, overexpression of p55PIK increased tumor angiogenesis in vivo and in vitro. Moreover, data indicated enhanced HIF-1α expression by p55PIK-PI3K depended on its ability to activate NF-кB signaling pathways, especially to increase the phosphorylation of p65 subunits of NF-κB. Our study suggested that p55PIK-PI3K was essential in regulating cancer cell-mediated angiogenesis and contributed to tumor growth and that the p55PIK provides a potential and specific target for new anti-angiogenesis drug development.

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Acknowledgments

This study was supported by grants of foundation of “973” Program (No. 2009CB521802), National Natural Science foundation (No. 30872472, No.30973496, No.81172512, No.81272278, and No.31000612). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

Authors declare no competing financial interests.

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Authors and Affiliations

  1. Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China

    Guihua Wang, Cheng Chen, Rui Yang, Xiaonian Cao, Senyan Lai, Xuelai Luo, Xianmin Xia & Junbo Hu

  2. Department of Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yongdong Feng & Jianping Gong

Authors
  1. Guihua Wang
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  2. Cheng Chen
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  3. Rui Yang
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  4. Xiaonian Cao
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  6. Xuelai Luo
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  7. Yongdong Feng
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  9. Jianping Gong
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  10. Junbo Hu
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Corresponding authors

Correspondence to Jianping Gong or Junbo Hu.

Additional information

Guihua Wang and Cheng Chen contributed equally to this work.

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Wang, G., Chen, C., Yang, R. et al. p55PIK-PI3K stimulates angiogenesis in colorectal cancer cell by activating NF-κB pathway. Angiogenesis 16, 561–573 (2013). https://doi.org/10.1007/s10456-013-9336-y

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  • DOI: https://doi.org/10.1007/s10456-013-9336-y

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