Raykhel, I., Moafi, F., Myllymäki, S., Greciano, P., Matlin, K., Moyano, J., Manninen, A., Myllyharju, J. (2018) BAMBI is a novel HIF1-dependent modulator of TGFβ-mediated disruption of cell polarity during hypoxia. Journal of Cell Science, 131 (10), jcs210906. doi:10.1242/jcs.210906
BAMBI is a novel HIF1-dependent modulator of TGFβ-mediated disruption of cell polarity during hypoxia
|Author:||Raykhel, Irina1; Moafi, Fazeh1; Myllymäki, Satu M.1;|
1Oulu Center for Cell-Matrix Research, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu
2Department of Surgery (Section of Research), University of Chicago
|Online Access:||PDF Full Text (PDF, 10.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201902084425
Company of Biologists,
|Publish Date:|| 2019-05-23
Hypoxia and loss of cell polarity are common features of malignant carcinomas. Hypoxia-inducible factor 1 (HIF1) is the major regulator of cellular hypoxia response and mediates the activation of ∼300 genes. Increased HIF1 signaling is known to be associated with epithelial–mesenchymal transformation. Here, we report that hypoxia disrupts polarized epithelial morphogenesis of MDCK cells in a HIF1α-dependent manner by modulating the transforming growth factor-β (TGFβ) signaling pathway. Analysis of potential HIF1 targets in the TGFβ pathway identified the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transmembrane glycoprotein related to the type I receptors of the TGFβ family, whose expression was essentially lost in HIF1-depleted cells. Similar to what was observed in HIF1-deficient cells, BAMBI-depleted cells failed to efficiently activate TGFβ signaling and retained epithelial polarity during hypoxia. Taken together, we show that hypoxic conditions promote TGFβ signaling in a HIF1-dependent manner and BAMBI is identified in this pathway as a novel HIF1-regulated gene that contributes to hypoxia-induced loss of epithelial polarity.
Journal of cell science
This work was supported Academy of Finland Research Council for Health grants [114344 (J.M.), 296498 (J.M.), 135560 (A.M.), 263770 (A.M.)] and Academy of Finland Center of Excellence 2012-2017 grant (251314 to J.M., A.M.), Sigrid Juséliuksen Säätiö (J.M.), Jane ja Aatos Erkon Säätiö (J.M.) and FibroGen Inc. (J.M.).
|Academy of Finland Grant Number:||
114344 (Academy of Finland Funding decision)
296498 (Academy of Finland Funding decision)
135560 (Academy of Finland Funding decision)
263770 (Academy of Finland Funding decision)
251314 (Academy of Finland Funding decision)
© 2018. Published by The Company of Biologists Ltd.