Banca de DEFESA: GABRIELA NOHEMI NÚÑEZ ESTEVES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : GABRIELA NOHEMI NÚÑEZ ESTEVES
DATE: 28/11/2023
TIME: 09:00
LOCAL: Online via Google Meet (Link da videochamada: https://meet.google.com/zer-oxkf-jfq)
TITLE:

Na⁺/Ca²⁺ Exchanger (NCX) and Ca²⁺ homeostasis in human melanoma model cells with the B-RAF^V600E and NRAS^Q61R mutations

PAGES: 75
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUBÁREA: Metabolismo e Bioenergética
SUMMARY:

Calcium is a ubiquitous intracellular second messenger, playing central roles in the regulation of several biological processes. Alterations in Ca²⁺ homeostasis and signaling are an important feature of tumor cells to acquire proliferative and survival advantages, which include structural and functional changes in storage capacity, channels, and pumps. Here,we investigated the differences in Ca²⁺ homeostasis in vemurafenib-responsive and nonresponsive melanoma cells. Also, the expression of the Na⁺/Ca²⁺ exchanger (NCX) and the impact of its inhibition were studied. For this, it was used BRAF^V600E (SK-MEL-19) and NRAS^Q6IR (SK-MEL-147) mutated human melanoma cells. The intracellular Ca²⁺chelator BAPTA-AM decreased the viability of SK-MEL-147 but not of SK-MEL-19 and EGTA sensitized NRAS^Q6IR -mutated cells to vemurafenib. These cells also presented a smaller response to thapsargin and ionomycin regarding the cytosolic Ca²⁺ levels in relation to SK-MEL-19, which was associated to an increased expression of NCX1, NO basal levels, and sensitivity to NCX
inhibitors. These data highlight the differences between BRAF^V600E and NRAS^Q6IR - mutated melanoma cells in response to Ca²⁺ stimuli and point to the potential combination of clinically used chemotherapeutic drugs, including vemurafenib, with NCX inhibitors as a new therapeutic strategy to the treatment of melanoma.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1674592 - TIAGO RODRIGUES
Membro Titular - Examinador(a) Interno ao Programa - 1061225 - CRISTINA RIBAS FURSTENAU
Membro Titular - Examinador(a) Externo ao Programa - 1669152 - DANIEL CARNEIRO CARRETTIERO
Membro Titular - Examinador(a) Externo à Instituição - LETÍCIA SILVA FERRAZ - UFRJ
Membro Titular - Examinador(a) Externo à Instituição - DEBORA CRISTINA DAMASCENO MEIRELLES DOS SANTOS - UNESP
Membro Suplente - Examinador(a) Interno ao Programa - 1640114 - MARCELA SORELLI CARNEIRO RAMOS
Membro Suplente - Examinador(a) Externo à Instituição - IVARNE LUIS DOS SANTOS TERSARIAL - UNIFESP
Membro Suplente - Examinador(a) Externo à Instituição - DENISE COSTA ARRUDA - UMC