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Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization

Canesin, G ; Cuevas, E P ; Santos, V ; López-Menéndez, C ; Moreno-Bueno, G ; Huang, Y ; Csiszar, K ; Portillo, F ; Peinado, H ; Lyden, D ; Cano, A

Oncogene, 2015-02, Vol.34 (8), p.951-964 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization
Autor: Canesin, G ; Cuevas, E P ; Santos, V ; López-Menéndez, C ; Moreno-Bueno, G ; Huang, Y ; Csiszar, K ; Portillo, F ; Peinado, H ; Lyden, D ; Cano, A
Assuntos: Amino Acid Oxidoreductases - physiology ; Animals ; Bone marrow ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cadherins - genetics ; Cell migration ; Cell Movement - genetics ; Cells, Cultured ; Cellular biology ; Colonization ; Dogs ; E-cadherin ; Epithelial-Mesenchymal Transition - genetics ; Female ; Fibronectin ; Gene Expression Regulation, Neoplastic ; Gene regulation ; Gene Silencing ; Granulocyte-macrophage colony-stimulating factor ; HEK293 Cells ; Helix-loop-helix proteins (basic) ; Humans ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - secondary ; Lysyl oxidase ; Mesenchyme ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Neoplasm Metastasis - genetics ; Osteoprogenitor cells ; Progenitor cells ; Studies ; Transcription Factor 3 - physiology ; Transcription factors ; Tumor cells ; Tumor necrosis factor-α
É parte de: Oncogene, 2015-02, Vol.34 (8), p.951-964
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Epithelial-mesenchymal transition (EMT) has been associated with increased aggressiveness and acquisition of migratory properties providing tumor cells with the ability to invade into adjacent tissues. Downregulation of E-cadherin, a hallmark of EMT, is mediated by several transcription factors (EMT-TFs) that act also as EMT inducers, among them, Snail1 and the bHLH transcription factor E47. We previously described lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, as a Snail1 regulator and EMT inducer. Here we show that LOXL2 is also an E47-interacting partner and functionally collaborates in the repression of E-cadherin promoter. Loss and gain of function analyses combined with in vivo studies in syngeneic breast cancer models demonstrate the participation of LOXL2 and E47 in tumor growth and their requirement for lung metastasis. Furthermore, LOXL2 and E47 contribute to early steps of metastatic colonization by cell and noncell autonomous functions regulating the recruitment of bone marrow progenitor cells to the lungs and by direct transcriptional regulation of fibronectin and cytokines TNFα, ANG-1 and GM-CSF. Moreover, fibronectin and GM-CSF proved to be necessary for LOXL2/E47-mediated modulation of tumor growth and lung metastasis.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization

Canesin, G ; Cuevas, E P ; Santos, V ; López-Menéndez, C ; Moreno-Bueno, G ; Huang, Y ; Csiszar, K ; Portillo, F ; Peinado, H ; Lyden, D ; Cano, A

England: Nature Publishing Group

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