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The ZNF304-integrin axis protects against anoikis in cancer

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Listed:
  • Burcu Aslan

    (University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center)

  • Paloma Monroig

    (University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center
    University of Puerto Rico School of Medicine)

  • Ming-Chuan Hsu

    (University of Texas MD Anderson Cancer Center
    National Institute of Cancer Research, National Health Research Institutes)

  • Guillermo Armaiz Pena

    (University of Texas MD Anderson Cancer Center)

  • Cristian Rodriguez-Aguayo

    (University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center)

  • Vianey Gonzalez-Villasana

    (University of Texas MD Anderson Cancer Center)

  • Rajesha Rupaimoole

    (Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Archana Sidalaghatta Nagaraja

    (Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Selanere Mangala

    (Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Hee-Dong Han

    (School of Medicine, Konkuk University)

  • Erkan Yuca

    (University of Texas MD Anderson Cancer Center)

  • Sherry Y. Wu

    (University of Texas MD Anderson Cancer Center)

  • Cristina Ivan

    (Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Tyler J. Moss

    (University of Texas MD Anderson Cancer Center)

  • Prahlad T. Ram

    (University of Texas MD Anderson Cancer Center)

  • Huamin Wang

    (University of Texas MD Anderson Cancer Center)

  • Alexandra Gol-Chambers

    (University of Texas MD Anderson Cancer Center)

  • Ozgur Ozkayar

    (University of Texas MD Anderson Cancer Center
    Hacettepe University School of Medicine)

  • Pinar Kanlikilicer

    (University of Texas MD Anderson Cancer Center)

  • Enrique Fuentes-Mattei

    (University of Texas MD Anderson Cancer Center)

  • Nermin Kahraman

    (University of Texas MD Anderson Cancer Center)

  • Sunila Pradeep

    (University of Texas MD Anderson Cancer Center)

  • Bulent Ozpolat

    (University of Texas MD Anderson Cancer Center)

  • Susan Tucker

    (University of Texas MD Anderson Cancer Center)

  • Mien-Chie Hung

    (University of Texas MD Anderson Cancer Center
    Center for Molecular Medicine and Institute of Cancer Biology, China Medical University)

  • Keith Baggerly

    (Hacettepe University School of Medicine)

  • Geoffrey Bartholomeusz

    (University of Texas MD Anderson Cancer Center)

  • George Calin

    (University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Anil K. Sood

    (Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Gabriel Lopez-Berestein

    (University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

Abstract

Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.

Suggested Citation

  • Burcu Aslan & Paloma Monroig & Ming-Chuan Hsu & Guillermo Armaiz Pena & Cristian Rodriguez-Aguayo & Vianey Gonzalez-Villasana & Rajesha Rupaimoole & Archana Sidalaghatta Nagaraja & Selanere Mangala & , 2015. "The ZNF304-integrin axis protects against anoikis in cancer," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8351
    DOI: 10.1038/ncomms8351
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    Cited by:

    1. Yue Yan & Binlong Chen & Qingqing Yin & Zenghui Wang & Ye Yang & Fangjie Wan & Yaoqi Wang & Mingmei Tang & Heming Xia & Meifang Chen & Jianxiong Liu & Siling Wang & Qiang Zhang & Yiguang Wang, 2022. "Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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