The inflammatory cytokine TNF contributes with RAC3-induced malignant transformation

MILENI SOARES MACHADO; FRANCISCO DAMIÁN ROSA; ALEJANDRO J. URTREGER; LAURA CAROLINA PANELO; GABRIELA INÉS MARINO; MÓNICA ALEJANDRA COSTAS; MARÍA CECILIA LIRA; MARÍA FERNANDA RUBIO

Mar del Plata, Argentina.

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

RAC3 is a coactivator of steroid receptors and transcription factorsand an important oncogene in tumor development. We havepreviously demonstrated that inflammatory cytokines increase theRAC3 expression and that high levels of this molecule could transformnon-tumor cells into cancer stem cells. The aim of this workwas to investigate if the inflammatory cytokine TNF could contributeto RAC3 transforming effect, maintaining or increasing stem properties. HEK293 cells (human embryonic kidney) overexpressingRAC3 (tumor) or not (non-tumoral) and other tumor cell lines (HeLaand T47D, silencing or not RAC3) were stimulated with TNF (10ng/ml) or vehicle and analyzed for their mesenchymal properties,migratory, invasive behavior and signals that contribute to the stemphenotype. We found that TNF potentiated the RAC3 overexpressioneffects, increasing the mesenchymal phenotype, through thedecrease of E-cadherin (p