Cx26 Drives Self-renewal in Triple-negative Breast Cancer Via Interaction with NANOG and Focal Adhesion Kinase

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Feb 10

PMID 29422613

Citations 51

Authors

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 Liu

Ofer Reizes

Justin D Lathia

Affiliations

Soon will be listed here.

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.

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