The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia
Open accessAbstract
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.
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1 retracted
Lysyl oxidase is essential for hypoxia-induced metastasis
Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhöfer, N., Kong, C., Le, Q.-T., Chi, J.-T. A., Jeffrey, S. S., & Giaccia, A. J. (2006) · Nature · doi:10.1038/nature04695 · Cited by 1,309
RetractedTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Self-citationHypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
Peinado, H., Olmeda, D., & Cano, A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2131 · Cited by 3,121
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Direct regulation of TWIST by HIF-1α promotes metastasis
Yang, M.-H., Wu, M.-Z., Chiou, S.-H., Chen, P.-M., Chang, S.-Y., Liu, C.-J., Teng, S.-C., & Wu, K.-J. (2008) · Nature Cell Biology · doi:10.1038/ncb1691 · Cited by 1,345
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Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition
Higgins, D. F., Kimura, K., Bernhardt, W. M., Shrimanker, N., Akai, Y., Hohenstein, B., Saito, Y., Johnson, R. S., Kretzler, M., Cohen, C. D., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30487 · Cited by 976
Self-citationRaval, R. R., Lau, K. W., Tran, M. G. B., Sowter, H. M., Mandriota, S. J., Li, J.-L., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5675-5686.2005 · Cited by 940
Cited by
Hypoxia and the extracellular matrix: drivers of tumour metastasis
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3726 · Cited by 1,520
The hypoxic tumour microenvironment
Petrova, V., Annicchiarico-Petruzzelli, M., Melino, G., & Amelio, I. (2018) · Oncogenesis · doi:10.1038/s41389-017-0011-9 · Cited by 1,019
Emami Nejad, A., Najafgholian, S., Rostami, A., Sistani, A., Shojaeifar, S., Esparvarinha, M., Nedaeinia, R., Haghjooy Javanmard, S., Taherian, M., Ahmadlou, M., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-020-01719-5 · Cited by 693
Hypoxia-inducible factors: cancer progression and clinical translation
Wicks, E. E., & Semenza, G. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci159839 · Cited by 580
The Extracellular Matrix Modulates the Metastatic Journey
Kai, F., Drain, A. P., & Weaver, V. M. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.03.026 · Cited by 537
Metadata
- Authors
- Schietke, R., Warnecke, C., Wacker, I., Schödel, J., Mole, D. R., Campean, V., Amann, K., Goppelt-Struebe, M., Behrens, J., Eckardt, K.-U., & Wiesener, M. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 285
- Issue
- 9
- Pages
- 6658-6669
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2161031052
- Cited by
- 253
- References
- 19
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia. https://app.cochat.ai/papers/10.1074/jbc.m109.042424
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- Schietke, R., Warnecke, C., Wacker, I., Schödel, J., Mole, D. R., Campean, V., Amann, K., Goppelt-Struebe, M., Behrens, J., Eckardt, K.-U., & Wiesener, M. S. (2010). The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.042424
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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