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Cancer and epithelial plasticity: new clues to understand metastasis

AutorCano, Amparo
Fecha de publicación2015
CitaciónXXXVIII Congreso de la SEBBM (2015)
ResumenMetastasis is a complex process involving several key steps from local invasion of tumor cells to their fi nal colonization of distant organs. In carcinomas, epithelial plasticity [i.e., epithelial-mesenchymal transition (EMT) and the reverse mesenchymal-epithelial transition (MET) processes] has emerged as a key regulator of several metastatic steps. Since the initial discovery of Snail1 as an EMT transcription factor (EMT-TF) essential for regulation of EMT, including post-transcriptional regulation of Snail and other EMT-TFs during tumor progression. We initially described LOXL2 (lysyl oxidase like-2) as a posttranslational regulator of Snail1 and an EMT inducer. LOXL2 belongs to the lysyl oxidase family of secreted proteins involved in the covalent crosslinking of different components of the Extracellular Matrix (ECM). However, LOXL2 is involved in a wide range of intracellular functions including transcriptional repression and chromatin remodeling. LOXL2 is a prognostic factor in squamous cell carcinoma (SCC) and associated to metastasis in basal-like breast carcinomas. To get further insights into LOXL2 multifunctional capability in tumorigenesis and metastasis, we have generated conditional gain- and loss-of-function mouse models for Loxl2 that are being studied in several tumor contexts, such as mouse skin carcinogenesis (a model of SCC) and PyMT breast cancer model. The data obtained indicate a key role of Loxl2 in the negative regulation of epidermal differentiation of SCC through repression of the Notch pathway, thus favoring malignant progression. In PyMT breast cancer Loxl2 plays a prominent role in lung metastasis directly contributing to the generation of the pre-metastatic niche, independent of changes in ECM stiffness. These data support a key action of intracellular LOXL2 in the regulation of epithelial plasticity and metastasis in highly relevant preclinical models.
DescripciónResumen del trabajo presentado al XXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Valencia del 7 al 10 de septiembre de 2015.
Aparece en las colecciones: (IIBM) Comunicaciones congresos
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