| Texto completo | |
| Autor(es): |
Almeida, Luciana O.
;
Silva, Luan Cesar
;
Emerick, Carolina
;
dos Santos, Juliana Amorim
;
Castilho, Rogerio M.
;
Squarize, Cristiane H.
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ARCHIVES OF ORAL BIOLOGY; v. 157, p. 9-pg., 2023-11-06. |
| Resumo | |
Objective: Emerging evidence suggests that the modest response of head and neck squamous cell carcinoma (HNSCC) to treatment is associated with cancer stem cells (CSC). However, the signaling pathways that play a role in HNSCC CSC maintenance and therapy response are not well-understood. In this study, we investigate the response of CSCs to phosphatase and tensin homolog (PTEN) modulation and its potential dependency on the mammalian target of rapamycin (mTOR) signaling.Design: PTEN deficiency was stably induced using short hairpin RNA (shRNA). Downregulation of RPTOR/ mTORC1 and RICTOR/mTORC2 was achieved using small interfering RNA (siRNA). CSCs were evaluated through tumorsphere formation and were classified into various subtypes: parasphere, merosphere, and holosphere. We investigated the effect of rapamycin on CSC properties in both control and PTEN-deficient HNSCC cells.Results: PTEN deficiency led to an accumulation of CSCs and enhanced a favorable response to rapamycin treatment. The viability of HNSCC CSCs was dependent on mTOR signaling. Deficiencies in both mTORC1 and mTORC2 reduced the number of CSCs. However, CSCs with PTEN deficiency had a greater reliance on mTORC1 signaling. Interestingly, when considering CSC subtypes, a deficiency in mTORC2 led to an increased number of paraspheres in both the control and PTEN-deficient groups.Conclusions: Loss of PTEN signaling increased the HNSCC CSC population, which can be targeted by rapamycin. However, the mTORC2 deficiency can induce a problematic selection of paraspheres CSCs subtype. (AU) | |
| Processo FAPESP: | 21/13381-9 - Usando bibliotecas de pequenas moléculas e triagem de alto rendimento para identificar novos compostos inibitórios para o tratamento de carcinomas mucoepidermóides das glândulas salivares |
| Beneficiário: | Luan César da Silva |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |
| Processo FAPESP: | 19/06597-5 - Disrupção da resistência tumoral através de terapia direcionada a depleção de células tronco tumorais em Carcinomas Mucoepidermoides Salivares |
| Beneficiário: | Luan César da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |