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

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, Luke A. Torre-Healy, Alvaro G. Alvarado, Awad Jarrar, Andrew Wiechert, Valery Adorno-Cruz, Paul L. Fox, Benjamin C. Calhoun, Jun Lin Guan, Huiping LiuOfer Reizes*, Justin D. Lathia

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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.

Original languageEnglish (US)
Article number578
JournalNature communications
Issue number1
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General
  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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