LOXL1 is regulated by Integrin alpha11 and promotes Non-Small Cell Lung Cancer tumorigenicity
Integrin alpha11, a stromal collagen receptor, promotes tumor growth and metastasis of non-small cell lung cancer (NSCLC) and is associated with the regulation of collagen stiffness in the tumor stroma. We have previously reported that lysyl oxidase like-1 (LOXL1), a matrix cross-linking enzyme, is down-regulated in integrin alpha11-deficient mice. In the present study, we investigated the relationship between LOXL1 and integrin alpha11, and the role of LOXL1 in NSCLC tumorigenicity. Our results show that the expression of LOXL1 and integrin alpha11 was correlated in three lung adenocarcinoma patient datasets and that integrin alpha11 indeed regulated LOXL1 expression in stromal cells. Using cancer-associated fibroblast (CAF) with either a knockdown or overexpression of LOXL1, we demonstrated a role for LOXL1 in collagen matrix remodeling and collagen fiber alignment in vitro and in vivo in a NSCLC xenograft model. As a consequence of collagen reorganization in NSCLC tumor stroma, we showed that LOXL1 supported tumor growth and progression. Our findings demonstrate that stromal LOXL1, under regulation of integrin alpha11, is a determinant factor of NSCLC tumorigenesis and may be an interesting target in this disease.
|ISBN||2072-6694 (Print) 2072-6694|
|Authors||Zeltz, C.; Pasko, E.; Cox, T. R.; Navab, R.; Tsao, M. S.|
|Responsible Garvan Author||A/Prof Thomas Cox|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/31121900|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/14975|