BRAF inhibition diminishes cell viability via PKCα in thyroid cancer cells

MATEO N CAMPOS HAEDO; DIAZ FALQUE MC; JOHANNA DIAZ ALBUJA; PERONA M; DEBERNARDI MM; CAYROL MF; BARREIRO ARCOS ML; JUVENAL GJ; CREMASCHI GA; ROSEMBLIT C

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias SAIC, SAI, SAFIS; 2020

Sociedad Argentina de Investigaciones Clínicas

Thyroid carcinoma (TC) is the most common endocrine neoplasia.Its incidence has increased in the last 40 years worldwide. It comprisesa group of tumors of different lineage and biological behavior.About half of TC are driven by an acquired activating mutation inthe BRAF oncogene. While targeted therapies have improved outcomesin melanoma patients, most TC patients become resistant orrecur suggesting that new or additive non-cross-reactive therapiesare needed. We have previously shown that PKCa mediates TSHand thyroid hormones proliferative effects in TC. Recent evidenceindicates that together PKCa overexpression and BRAF mutationshould contribute to tumorigenesis and resistance to anticancertherapies. We found that by inhibiting BRAF expression with RNAi inanaplastic TC cells with BRAF mutation, PKCa expression decreasesas well, suggesting that the latter is found downstream of BRAF.Furthermore, a decrease in the expression of the cell proliferationmarker PCNA was observed in BRAF-depleted cells by westernblot analysis. Also, TC cells were sensitive to increasing doses ofthe BRAF inhibitor widely used in the clinic vemurafenib/PLX4032in a dose-dependent manner (p