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Publication : Lysyl Oxidase-like Protein LOXL2 Promotes Lung Metastasis of Breast Cancer.

First Author  Salvador F Year  2017
Journal  Cancer Res Volume  77
Issue  21 Pages  5846-5859
PubMed ID  28720577 Mgi Jnum  J:248913
Mgi Id  MGI:6094001 Doi  10.1158/0008-5472.CAN-16-3152
Citation  Salvador F, et al. (2017) Lysyl Oxidase-like Protein LOXL2 Promotes Lung Metastasis of Breast Cancer. Cancer Res 77(21):5846-5859
abstractText  The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling. In support of this likelihood, cellular and molecular analyses revealed an association of LOXL2 action with elevated levels of the EMT regulatory transcription factor Snail1 and expression of several cytokines that promote premetastatic niche formation. Taken together, our findings established a pathophysiologic role and new function for LOXL2 in breast cancer metastasis. Cancer Res; 77(21); 5846-59. (c)2017 AACR.
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