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Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase

Author

Listed:
  • Praveena S. Thiagarajan

    (Cleveland Clinic
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University)

  • Maksim Sinyuk

    (Cleveland Clinic)

  • Soumya M. Turaga

    (Cleveland Clinic)

  • Erin E. Mulkearns-Hubert

    (Cleveland Clinic)

  • James S. Hale

    (Cleveland Clinic)

  • Vinay Rao

    (Cleveland Clinic)

  • Abeba Demelash

    (Cleveland Clinic)

  • Caner Saygin

    (Cleveland Clinic)

  • Arnab China

    (Cleveland Clinic)

  • Tyler J. Alban

    (Cleveland Clinic
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University)

  • Masahiro Hitomi

    (Cleveland Clinic
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University)

  • Luke A. Torre-Healy

    (Cleveland Clinic)

  • Alvaro G. Alvarado

    (Cleveland Clinic)

  • Awad Jarrar

    (Cleveland Clinic)

  • Andrew Wiechert

    (Cleveland Clinic)

  • Valery Adorno-Cruz

    (Case Comprehensive Cancer Center
    Case Western Reserve University
    Northwestern University School of Medicine)

  • Paul L. Fox

    (Cleveland Clinic
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
    Case Comprehensive Cancer Center)

  • Benjamin C. Calhoun

    (Cleveland Clinic)

  • Jun-Lin Guan

    (University of Cincinnati)

  • Huiping Liu

    (Case Comprehensive Cancer Center
    Case Western Reserve University
    Northwestern University School of Medicine)

  • Ofer Reizes

    (Cleveland Clinic
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
    Case Comprehensive Cancer Center)

  • Justin D. Lathia

    (Cleveland Clinic
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
    Case Comprehensive Cancer Center)

Abstract

Tumors adapt their phenotypes during growth and in response to therapies through dynamic changes in cellular processes. Connexin proteins enable such dynamic changes during development, and their dysregulation leads to disease states. The gap junction communication channels formed by connexins have been reported to exhibit tumor-suppressive functions, including in triple-negative breast cancer (TNBC). However, we find that connexin 26 (Cx26) is elevated in self-renewing cancer stem cells (CSCs) and is necessary and sufficient for their maintenance. Cx26 promotes CSC self-renewal by forming a signaling complex with the pluripotency transcription factor NANOG and focal adhesion kinase (FAK), resulting in NANOG stabilization and FAK activation. This FAK/NANOG-containing complex is not formed in mammary epithelial or luminal breast cancer cells. These findings challenge the paradigm that connexins are tumor suppressors in TNBC and reveal a unique function for Cx26 in regulating the core self-renewal signaling that controls CSC maintenance.

Suggested Citation

  • Praveena S. Thiagarajan & Maksim Sinyuk & Soumya M. Turaga & Erin E. Mulkearns-Hubert & James S. Hale & Vinay Rao & Abeba Demelash & Caner Saygin & Arnab China & Tyler J. Alban & Masahiro Hitomi & Luk, 2018. "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02938-1
    DOI: 10.1038/s41467-018-02938-1
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