SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9

Kazufumi Tanigawa, Masashi Maekawa, Takeshi Kiyoi, Jun Nakayama, Riko Kitazawa, Sohei Kitazawa, Kentaro Senba, Tomohiko Taguchi, Satoshi Akita, Motohira Yoshida, Kei Ishimaru, Yuji Watanabe, Shigeki Higashiyama

    Research output: Contribution to journalArticle

    Abstract

    Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High-level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.

    Original languageEnglish
    JournalJournal of Cellular Physiology
    DOIs
    Publication statusPublished - 2019 Jan 1

    Fingerprint

    Sorting Nexins
    Endothelial cells
    Integrins
    Colorectal Neoplasms
    Endothelial Cells
    Human Umbilical Vein Endothelial Cells
    Angiogenesis Inducing Agents
    Blood vessels
    Blood Vessels
    Tumors
    Angiogenic Proteins
    Intracellular Membranes
    Vascular Endothelial Growth Factor Receptor
    Cell proliferation
    Recycling
    Cell membranes
    Small Interfering RNA
    Cell Movement
    Neoplasms
    Membrane Proteins

    Keywords

    • angiogenesis
    • colorectal cancer
    • endothelial cells
    • integrin β1
    • sorting nexin 9

    ASJC Scopus subject areas

    • Physiology
    • Clinical Biochemistry
    • Cell Biology

    Cite this

    SNX9 determines the surface levels of integrin β1 in vascular endothelial cells : Implication in poor prognosis of human colorectal cancers overexpressing SNX9. / Tanigawa, Kazufumi; Maekawa, Masashi; Kiyoi, Takeshi; Nakayama, Jun; Kitazawa, Riko; Kitazawa, Sohei; Senba, Kentaro; Taguchi, Tomohiko; Akita, Satoshi; Yoshida, Motohira; Ishimaru, Kei; Watanabe, Yuji; Higashiyama, Shigeki.

    In: Journal of Cellular Physiology, 01.01.2019.

    Research output: Contribution to journalArticle

    Tanigawa, K, Maekawa, M, Kiyoi, T, Nakayama, J, Kitazawa, R, Kitazawa, S, Senba, K, Taguchi, T, Akita, S, Yoshida, M, Ishimaru, K, Watanabe, Y & Higashiyama, S 2019, 'SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9' Journal of Cellular Physiology. https://doi.org/10.1002/jcp.28346
    Tanigawa, Kazufumi ; Maekawa, Masashi ; Kiyoi, Takeshi ; Nakayama, Jun ; Kitazawa, Riko ; Kitazawa, Sohei ; Senba, Kentaro ; Taguchi, Tomohiko ; Akita, Satoshi ; Yoshida, Motohira ; Ishimaru, Kei ; Watanabe, Yuji ; Higashiyama, Shigeki. / SNX9 determines the surface levels of integrin β1 in vascular endothelial cells : Implication in poor prognosis of human colorectal cancers overexpressing SNX9. In: Journal of Cellular Physiology. 2019.
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