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Hypoxia-Related Enzyme Essential for Tumor Metastasis

Study supports LOX as therapeutic target for metastatic disease

WEDNESDAY, April 26 (HealthDay News) -- The enzyme lysyl oxidase (LOX) is highly expressed in hypoxic human tumor cells and plays an essential role in metastasis, according to a report in the April 27 issue of Nature. The protein could be a new target for potential cancer therapies.

For unknown reasons, hypoxia is associated with metastatic spread and poorer cancer prognosis. In the study, Amato J. Giaccia, Ph.D., from Stanford University School of Medicine in Stanford, Calif., and colleagues found that LOX expression is higher in hypoxic human breast and head and neck tumors, as previously shown, and correlates with poorer patient prognosis.

Targeting LOX in mice either genetically, or through use of chemical or antibody inhibitors, reduced or eliminated metastases to the lung and liver, and quelled invasive properties of hypoxic tumor cells in vitro. Mechanistically, the authors suspect LOX activity works by increasing adhesion and migration on extracellular matrix proteins through activation of focal adhesion kinase.

"We propose that hypoxia-induced LOX has a key function in tumor metastasis," the authors write. "Our data provide mechanistic evidence for hypoxia-driven metastasisÂ…and support the therapeutic targeting of LOX to prevent and treat metastatic disease."

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