BAMBI is a novel HIF1-dependent modulator of TGFβ-mediated disruption of cell polarity during hypoxia
Raykhel, Irina; Moafi, Fazeh; Myllymäki, Satu M.; Greciano, Patricia G.; Matlin, Karl S.; Moyano, Jose V.; Manninen, Aki; Myllyharju, Johanna (2018-05-23)
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
© 2018. Published by The Company of Biologists Ltd.
https://rightsstatements.org/vocab/InC/1.0/
https://urn.fi/URN:NBN:fi-fe201902084425
Tiivistelmä
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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