BioISI Post Graduate Seminars

Targeting RAC1-signaling to enhance iodide-related cancer therapy

Auditório da FCiências.ID, Lisboa

Por Márcia Faria (BioSYS PhD Student - FunGP).

The Sodium Iodide Symporter (NIS), responsible for active transport of iodide into thyroid cells, allows the use of radioactive iodine (RAI) as the systemic treatment of choice for thyroid cancer (TC) metastatic disease. Still, patients with advanced forms of TC sometimes lose the ability to respond to RAI therapy, which reduces their survival rates. NIS protein abundance and stabilization at the plasma membrane (PM) has been put forward as a major limiting factor for iodide uptake. Thus, in this study, we are currently investigating the impact of RAC1-signaling on NIS functional expression at the PM. We generated a TPC1 thyroid cancer cell line clone stably expressing a full-length NIS construct containing an extracellular triple HA tag. The PM levels of NIS upon interference with RAC1-signaling were assessed using surface protein biotinylation assays. Notably, treatment with the selective RAC1 inhibitor, EHT1864, induced a dramatic decrease (≈90%) on NIS overall and PM expression, while the overexpression of constitutively active RAC1 mutant produced the opposite result, increasing by over 2- fold NIS PM levels. To ascertain the potential impact of RAC1-signaling on the efficacy of iodide uptake, we used a non-radioactive iodide influx assay that showed a decreased iodide influx rate upon EHT1864 treatment. These results disclose an unequivocal association between RAC1-signaling and NIS posttranslational regulation.

17h00
BioISI - Instituto de Biossistemas e Ciências Integrativas