The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in Hypoxia: Insights into cellular transformation processes mediated by HIF-1

Schietke R, Warnecke C, Wacker I, Schödel J, Mole DR, Campean V, Amann KU, Goppelt-Strübe M, Behrens J, Eckardt KU, Wiesener MS (2010)

Publication Type: Journal article

Publication year: 2010

Journal

Journal of Biological Chemistry American Society for Biochemistry and Molecular Biology

Book Volume: 285

Pages Range: 6658-6669

Journal Issue: 9

DOI: 10.1074/jbc.M109.042424

Abstract

Hypoxia has been shown to promote tumor metastasis and lead to therapy resistance. Recent work has demonstrated that hypoxia represses E-cadherin expression, a hallmark of epithelial to mesenchymal transition, which is believed to amplify tumor aggressiveness. The molecular mechanism of E-cadherin repression is unknown, yet lysyl oxidases have been implicated to be involved. Gene expression of lysyl oxidase (LOX) and the related LOX-like 2 (LOXL2) is strongly induced by hypoxia. In addition to the previously demonstrated LOX, we characterize LOXL2 as a direct transcriptional target of HIF-1. We demonstrate that activation of lysyl oxidases is required and sufficient for hypoxic repression of E-cadherin, which mediates cellular transformation and takes effect in cellular invasion assays. Our data support a molecular pathway from hypoxia to cellular transformation. It includes up-regulation of HIF and subsequent transcriptional induction of LOX and LOXL2, which repress E-cadherin and induce epithelial to mesenchymal transition. Lysyl oxidases could be an attractive molecular target for cancers of epithelial origin, in particular because they are partly extracellular. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Authors with CRIS profile

Christina Warnecke Department of Medicine 4 – Nephrology and Hypertension Ingrid Wacker Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung) Kerstin Ute Amann Professur für Nephropathologie Margarete Goppelt-Strübe Department of Medicine 4 – Nephrology and Hypertension Jürgen Behrens Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung) Kai-Uwe Eckardt Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

University of Oxford GB United Kingdom (GB)

How to cite

APA:

Schietke, R., Warnecke, C., Wacker, I., Schödel, J., Mole, D.R., Campean, V.,... Wiesener, M.S. (2010). The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in Hypoxia: Insights into cellular transformation processes mediated by HIF-1. Journal of Biological Chemistry, 285(9), 6658-6669. https://doi.org/10.1074/jbc.M109.042424

MLA:

Schietke, Ruth, et al. "The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in Hypoxia: Insights into cellular transformation processes mediated by HIF-1." Journal of Biological Chemistry 285.9 (2010): 6658-6669.

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