Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer.
Author: Moncho Amor, Verónica; Pintado Berninches, Laura; Ibáñez de Cáceres, Inmaculada; Martín Villar, Ester; Quintanilla, Miguel; Chakravarty, Probir; Cortes Sempere, María; Fernández Varas, Beatriz; Rodríguez Antolín, Carlos; De Castro, Javier; Sastre, Leandro; Perona, Rosario
Abstract: DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase
ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies
from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor
prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6.
In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell
migration, motility and tumor growth. We have found upregulation in the expression of several
genes involved in epithelial to mesenchymal transition (EMT) in NSCLC-DUSP6 depleted cells.
Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF- and
WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression
is upregulated in these cells and therefore a ecting cellular functions such as integrin mediated cell
adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5
and not ERK1/2 and TGF- via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor
suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert
poor outcome in NSCLC patients.
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