Targeting cancer stem cells by mTOR inhibition in human mucoepidermoid carcinoma (2017)
- Authors:
- Autor USP: NUNES, FABIO DAUMAS - FO
- Unidade: FO
- Subjects: CÉLULAS-TRONCO; CARCINOMA DE CÉLULAS ESCAMOSAS; SEGMENTAÇÃO
- Language: Português
- Abstract: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. We have recently reported that cancer stem cells drive the tumorigenic process of MEC. Our objective was to investigate the effect of mTOR inhibition in the pathobiology of cancer stem cells in MEC. We performed immunohistochemistry for p-mTOR/p-S6K-1 in an annotated panel of human MEC and correlated results to patient outcomes, and performed co-immunoflorescence for ALDH/p-mTOR in human MEC. Mechanistic studies were performed in 3 human MEC cell lines with inhibitors of the mTOR signaling pathway. We performed cytotoxic, western blot, flow cytometry for ALDH/CD44, salispheres and apoptosis assays. In addition, we performed genetic silencing of mTOR, and in vivo assays with chemical and genetic mTOR inhibitors. We observed that mTOR pathway is constitutively active in MEC cancer stem cells, and that high mTOR expression correlates with poor patient prognosis (p=0.002941). mTOR inhibition led to loss of self-renewal and decrease fraction of cancer stem cells in vitro (p<0.05) and in vivo (p=0.0027). A decrease in p-AKT upon mTOR inhibition indicated involvement of mTORC2. mTOR inhibition with Temsirolimus caused MEC tumor regression in vivo (p < 0.0001) and mTOR silencing (shRNA) caused slowdown of tumor growth over 90 day follow-up (p<0.0001). Collectively, these results demonstrated that mTOR signaling is required for the survival of MEC cancer stem cells, and suggested that patients with mucoepidermoid carcinoma might benefit from therapeutic inhibition of mTOR.
- Imprenta:
- Source:
- Título: Brazilian Oral Research
- ISSN: 1807-3107
- Volume/Número/Paginação/Ano: v. 31, supl. 2, p. 49, res. HA016, 2017
- Conference titles: Proceedings of the SBPqO Annual Meeting
-
ABNT
ANDRADE, N. P e NUNES, F. D e NÖR, J. E. Targeting cancer stem cells by mTOR inhibition in human mucoepidermoid carcinoma. Brazilian Oral Research. São Paulo: SBPqO. . Acesso em: 12 jan. 2026. , 2017 -
APA
Andrade, N. P., Nunes, F. D., & Nör, J. E. (2017). Targeting cancer stem cells by mTOR inhibition in human mucoepidermoid carcinoma. Brazilian Oral Research. São Paulo: SBPqO. -
NLM
Andrade NP, Nunes FD, Nör JE. Targeting cancer stem cells by mTOR inhibition in human mucoepidermoid carcinoma. Brazilian Oral Research. 2017 ; 31 49.[citado 2026 jan. 12 ] -
Vancouver
Andrade NP, Nunes FD, Nör JE. Targeting cancer stem cells by mTOR inhibition in human mucoepidermoid carcinoma. Brazilian Oral Research. 2017 ; 31 49.[citado 2026 jan. 12 ] - Oral lichen planus: a histophatological study [Carta]
- Rabdomiossarcoma embrionário em mucosa jugal
- DNA methyltransferase immunohistochemical expression in odontogenic tumours
- CLRD é lançada com foco em indexação internacional [Editorial]
- Expressão do RNA mensageiro dos genes HOX em linhagens celulares de carcinomas epidermoides de cabeça e pescoço
- Expressão de transcritos do gene HOXA7 em carcinomas epidermóide de boca por RT-PCR e hibridização in situ
- Imunoexpressão de DNMT3B na carcinogênese de boca
- Evaluation of the genomic DNA extracted from formalin-fixed, paraffin-embedded oral samples archived for the past 40-years
- The homeobox HOXB13 is expressed in human minor salivary gland
- DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity
How to cite
A citação é gerada automaticamente e pode não estar totalmente de acordo com as normas
