PUBLICATION
Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit
- Authors
- Hatzold, J., Beleggia, F., Herzig, H., Altmüller, J., Nürnberg, P., Bloch, W., Wollnik, B., Hammerschmidt, M.
- ID
- ZDB-PUB-160531-1
- Date
- 2016
- Source
- eLIFE 5: e14277 (Journal)
- Registered Authors
- Hammerschmidt, Matthias, Hatzold, Julia
- Keywords
- cancer biology, developmental biology, stem cells, zebrafish
- MeSH Terms
-
- Animals
- Carcinoma, Basal Cell/physiopathology*
- Keratinocytes/enzymology*
- Keratinocytes/physiology*
- Osmotic Pressure
- Sodium-Potassium-Exchanging ATPase/deficiency
- Sodium-Potassium-Exchanging ATPase/metabolism*
- Zebrafish
- PubMed
- 27240166 Full text @ Elife
Citation
Hatzold, J., Beleggia, F., Herzig, H., Altmüller, J., Nürnberg, P., Bloch, W., Wollnik, B., Hammerschmidt, M. (2016) Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit. eLIFE. 5:e14277.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping