University of Oulu

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

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Author: Raykhel, Irina1; Moafi, Fazeh1; Myllymäki, Satu M.1;
Organizations: 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
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 10.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201902084425
Language: English
Published: Company of Biologists, 2018
Publish Date: 2019-05-23
Description:

Abstract

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.

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Series: Journal of cell science
ISSN: 0021-9533
ISSN-E: 1477-9137
ISSN-L: 0021-9533
Volume: 131
Issue: 10
Article number: jcs210906
DOI: 10.1242/jcs.210906
OADOI: https://oadoi.org/10.1242/jcs.210906
Subjects:
Funding: 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
296498
135560
263770
251314
Detailed Information: 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)
Dataset Reference: Supplementary information:
  http://jcs.biologists.org/lookup/doi/10.1242/jcs.210906.supplemental
Copyright information: © 2018. Published by The Company of Biologists Ltd.