Journal
EMBO JOURNAL
Volume 34, Issue 8, Pages 1090-1109Publisher
WILEY
DOI: 10.15252/embj.201489975
Keywords
epidermal differentiation; Loxl2 mouse models; male sterility; Notch1; squamous cell carcinoma
Categories
Funding
- Spanish Ministry of Economy and Innovation [SAF2010-21143, SAF2010-20175, SAF2013-44739-R, CONSOLIDER-INGENIO 2010 CSD2007-00017]
- AICR [12-1057]
- Spanish Instituto de Salud Carlos III [RETIC-RD12/0036/0007, RETICCRD12/0036/0054, PI13/00132]
- Comunidad de Madrid [S2010/BMD-2303, AECC-2011]
- CSIC
- Worldwide Cancer Research [12-1057] Funding Source: researchfish
Ask authors/readers for more resources
Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions. To explore the specific in vivo role of LOXL2 in physiological and tumor contexts, we generated conditional gain- and loss-of-function mouse models. Germ-line deletion of Loxl2 promotes lethality in half of newborn mice mainly associated to congenital heart defects, while Loxl2 overexpression triggers male sterility due to epididymal dysfunction caused by epithelial disorganization, fibrosis and acute inflammation. Remarkably, when challenged to chemical skin carcinogenesis, Loxl2-overexpressing mice increased tumor burden and malignant progression, while Loxl2-deficient mice exhibit the opposite phenotypes. Loxl2 levels in premalignant tumors negatively correlate with expression of epidermal differentiation markers and components of the Notch1 pathway. We show that LOXL2 is a direct repressor of NOTCH1. Additionally, we identify an exclusive expression pattern between LOXL2 and members of the canonical NOTCH1 pathway in human HNSCC. Our data identify for the first time novel LOXL2 roles in tissue homeostasis and support it as a target for SCC therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available