Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Apr 27;440(7088):1222-6.
doi: 10.1038/nature04695.

Lysyl oxidase is essential for hypoxia-induced metastasis

Janine T Erler  1 , Kevin L Bennewith, Monica Nicolau, Nadja Dornhöfer, Christina Kong, Quynh-Thu Le, Jen-Tsan Ashley Chi, Stefanie S Jeffrey, Amato J Giaccia
Affiliations

Lysyl oxidase is essential for hypoxia-induced metastasis

Janine T Erler et al. Nature. .

Retraction in

Abstract

Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell-cell or cell-matrix interactions) and the extended tumour microenvironment (for example vascularization). Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Significance of HIF-1α Expression and LOXL-2 Localization in Progression of Oral Squamous Cell Carcinoma.
    Bharti A, Urs AB, Kumar P. Bharti A, et al. Asian Pac J Cancer Prev. 2021 Feb 1;22(2):341-347. doi: 10.31557/APJCP.2021.22.2.341. Asian Pac J Cancer Prev. 2021. PMID: 33639646 Free PMC article.
  • A physical sciences network characterization of non-tumorigenic and metastatic cells.
    Physical Sciences - Oncology Centers Network; Agus DB, Alexander JF, Arap W, Ashili S, Aslan JE, Austin RH, Backman V, Bethel KJ, Bonneau R, Chen WC, Chen-Tanyolac C, Choi NC, Curley SA, Dallas M, Damania D, Davies PC, Decuzzi P, Dickinson L, Estevez-Salmeron L, Estrella V, Ferrari M, Fischbach C, Foo J, Fraley SI, Frantz C, Fuhrmann A, Gascard P, Gatenby RA, Geng Y, Gerecht S, Gillies RJ, Godin B, Grady WM, Greenfield A, Hemphill C, Hempstead BL, Hielscher A, Hillis WD, Holland EC, Ibrahim-Hashim A, Jacks T, Johnson RH, Joo A, Katz JE, Kelbauskas L, Kesselman C, King MR, Konstantopoulos K, Kraning-Rush CM, Kuhn P, Kung K, Kwee B, Lakins JN, Lambert G, Liao D, Licht JD, Liphardt JT, Liu L, Lloyd MC, Lyubimova A, Mallick P, Marko J, McCarty OJ, Meldrum DR, Michor F, Mumenthaler SM, Nandakumar V, O'Halloran TV, Oh S, Pasqualini R, Paszek MJ, Philips KG, Poultney CS, Rana K, Reinhart-King CA, Ros R, Semenza GL, Senechal P, Shuler ML, Srinivasan S, Staunton JR, Stypula Y, Subramanian H, Tlsty TD, Tormoen GW, Tseng Y, van Oudenaarden A, Verbridge SS, Wan JC, Weaver VM, Widom J, Will C, Wirtz D, Wojtkowiak J, Wu PH. Physical Sciences - Oncology Centers Network, et al. Sci Rep. 2013;3:1449. doi: 10.1038/srep01449. Sci Rep. 2013. PMID: 23618955 Free PMC article.
  • Localized hypoxia results in spatially heterogeneous metabolic signatures in breast tumor models.
    Jiang L, Greenwood TR, Artemov D, Raman V, Winnard PT Jr, Heeren RM, Bhujwalla ZM, Glunde K. Jiang L, et al. Neoplasia. 2012 Aug;14(8):732-41. doi: 10.1593/neo.12858. Neoplasia. 2012. PMID: 22952426 Free PMC article.
  • The extracellular matrix: a dynamic niche in cancer progression.
    Lu P, Weaver VM, Werb Z. Lu P, et al. J Cell Biol. 2012 Feb 20;196(4):395-406. doi: 10.1083/jcb.201102147. J Cell Biol. 2012. PMID: 22351925 Free PMC article. Review.
  • RHOBTB3 promotes proteasomal degradation of HIFα through facilitating hydroxylation and suppresses the Warburg effect.
    Zhang CS, Liu Q, Li M, Lin SY, Peng Y, Wu D, Li TY, Fu Q, Jia W, Wang X, Ma T, Zong Y, Cui J, Pu C, Lian G, Guo H, Ye Z, Lin SC. Zhang CS, et al. Cell Res. 2015 Sep;25(9):1025-42. doi: 10.1038/cr.2015.90. Epub 2015 Jul 28. Cell Res. 2015. PMID: 26215701 Free PMC article.
See all "Cited by" articles

Publication types

MeSH terms

Substances