Functional 1 Toll-like Receptor 4 Overexpression in Papillary Thyroid Cancer by MAPK/ERK-induced ETS1 Transcriptional Activity

PEYRET V; NAZAR M; MARTIN M; QUINTAR A; FERNANDEZ EA; GEYSELS R; FUZIWARA C; MONTESINOS MM; MALDONADO CA; SANTISTEBAN P; KIMURA E; PELLIZAS CG; NICOLA JP; MASINI-REPISO AM

MOLECULAR CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Lugar: Philadelphia; Año: 2018

1541-7786

merging evidence suggests that unregulated Toll-like receptors (TLRs) signaling promotes tumor survival34 signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillarythyroid carcinomas (PTCs) mainly harboring the BRAFV600E 35 mutation was studied. TLR4 was overexpressed in36 PTCs compared to non-neoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its37 lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. Inagreement, conditional BRAFV600E 38 expression in normal rat thyroid cells and mouse thyroid tissue39 upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC40 cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonistlipopolysaccharide (LPS). Of note, The Cancer Genome Atlas (TCGA) data analysis revealed that BRAFV600E41 -42 positive tumors with high TLR4 expression were associated w