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

PEYRET, VICTORIA; NAZAR, MAGALÍ; MARTÍN, MARIANO; QUINTAR, AMADO A.; FERNANDEZ, ELMER A.; GEYSELS, ROMINA C.; FUZIWARA, CESAR S.; MONTESINOS, MARÍA M.; MALDONADO, CRISTINA A.; SANTISTEBAN, PILAR; KIMURA, EDNA T.; PELLIZAS, CLAUDIA G.; NICOLA, JUAN P.; MASINI-REPISO, ANA M.

MOLECULAR CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Año: 2018 vol. 16 p. 833 - 833

1541-7786

merging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAFV600E mutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. In agreement, conditional BRAFV600E expression in normal rat thyroid cells and mouse thyroid tissue upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonist lipopolysaccharide. Of note, The Cancer Genome Atlas data analysis revealed that BRAFV600E-positive tumors with high TLR4 expression were associated wit