journal contribution
posted on 2023-03-31, 01:43 authored by Fernando Salvador, Alberto Martin, Celia López-Menéndez, Gema Moreno-Bueno, Vanesa Santos, Alberto Vázquez-Naharro, Patricia G. Santamaría, Saleta Morales, Pierre R. Dubus, Laura Muinelo-Romay, Rafael López-López, Jason C. Tung, Valerie M. Weaver, Francisco Portillo, Amparo Cano Collagen organization in metastatic lungs (Fig. S6) and Tenascin-C and fibronectin expression in primary tumors and lungs from PyMT mice with deregulated Loxl2
Funding
Spanish Ministry of Economy and Innovation
CONSOLIDER-INGENIO
Institute of Health Carlos III
CIBERONC
Worldwide Cancer Research
Comunidad de Madrid
JAE-CSIC
History
ARTICLE ABSTRACT
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. ©2017 AACR.
