Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

Hatzold J, Beleggia F, Herzig H, Altmüller J, Nürnberg P, Bloch W, Wollnik B, Hammerschmidt M

Elife 2016 May;5

PMID: 27240166

Abstract

Molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of one and the same gene as a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a thus far unrecognized contributor to tumor development and establish a novel paradigm of tumor suppression.

  • Upcoming Events

    1. “Collagen secretion in Health and Disease”

      June 26 @ 5:15 pm - 6:15 pm
    2. Women in Science and Society lecture with Prof. Susan E Quaggin

      July 1 @ 12:30 pm - 7:00 pm
    3. 4th Connector Meeting

      September 6 @ 3:00 pm - 6:30 pm
    4. 5th Connector Meeting

      November 8 @ 3:00 pm - 6:00 pm
  • News

© 2017 SFB 829

Durch die weitere Nutzung der Seite stimmst du der Verwendung von Cookies zu. Weitere Informationen

Die Cookie-Einstellungen auf dieser Website sind auf "Cookies zulassen" eingestellt, um das beste Surferlebnis zu ermöglichen. Wenn du diese Website ohne Änderung der Cookie-Einstellungen verwendest oder auf "Akzeptieren" klickst, erklärst du sich damit einverstanden.

Schließen