Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/44192 |
Resumo: | CNPq, CAPES and FAPESB (grant number APP0006/2016). |
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Mendes, Jéssica Mariane FerreiraValverde, Ludmila de FaroVidal, Manuela Torres AndionParedes, Bruno DiazCoelho, PauloAllahdadi, Kyan JamesColetta, Ricardo DellaSouza, Bruno Solano de FreitasRocha, Clarissa Araújo Gurgel2020-10-26T14:02:39Z2020-10-26T14:02:39Z2020MENDES, Jéssica Mariane Ferreira et al. Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences, 2020.1661-6596https://www.arca.fiocruz.br/handle/icict/4419210.3390/ijms21186487CNPq, CAPES and FAPESB (grant number APP0006/2016).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA,Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA,Brazil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Campinas State University. Department of Oral Diagnosis, School of Dentistry. Piracicaba, SP, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Department of Pathology, School of Medicine and School of Dentistry. Salvador, BA, Brazil.Background: Activation of the PI3K-AKT pathway controls most hallmarks of cancer, and the hedgehog (HH) pathway has been associated with oral squamous cell carcinoma (OSCC) development and progression. We hypothesized that fibroblast-derived insulin-like growth factor-1 (IGF-1) acts in oral squamous cell carcinoma (OSCC) cells, leading to the non-canonical activation of the HH pathway, maintaining AKT activity and promoting tumor aggressiveness. (2) Methods: Primary fibroblasts (MF1) were genetically engineered for IGF-1 overexpression (MF1-IGF1) and CRISPR/Cas9-mediated IGF1R silencing was performed in SCC-4 cells. SCC-4 cells were co-cultured with fibroblasts or incubated with fibroblast conditioned medium (CM) or rIGF-1 for functional assays and the evaluation of AKT and HH pathways. (3) Results: Gene expression analysis confirmed IGF-1 overexpression in MF1-IGF1 and the absence of IGF-1 expression in SCC-4, while elevated IGF1R expression was detected. IGF1R silencing was associated with decreased survival of SCC-4 cells. Ihh was expressed in both MF1 and MF1-IGF1, and increased levels of GLI1 mRNA were observed in SCC-4 after stimulation with CM-MF1. Activation of both PI3K-AKT and the HH pathway (GLI1, Ihh and SMO) were identified in SCC-4 cells cultured in the presence of MF1-IGF1-CM. rIGF-1 promoted tumor cell proliferation, migration, invasion and tumorsphere formation, whereas CM-MF1 significantly stimulated angiogenesis. (4) Conclusions: IGF-1 exerts pro-tumorigenic e ects by stimulating SCC-4 cell proliferation, migration, invasion and stemness. AKT and HH pathways were activated by IGF-1 in SCC-4, reinforcing its influence on the regulation of these signaling pathways.engMDPIIGF-1OuriçoAdenocarcinomaFator 1 de Crescimento de FibroblastosIGF-1HedgehogPI3K-AKTEffects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/44192/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALMendes, J.M.F. Effects....pdfMendes, J.M.F. Effects....pdfapplication/pdf4938240https://www.arca.fiocruz.br/bitstream/icict/44192/2/Mendes%2c%20J.M.F.%20Effects....pdf364195d606923e91c417b7e28f24a4f1MD52TEXTMendes, J.M.F. Effects....pdf.txtMendes, J.M.F. 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| dc.title.pt_BR.fl_str_mv |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| title |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| spellingShingle |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma Mendes, Jéssica Mariane Ferreira IGF-1 Ouriço Adenocarcinoma Fator 1 de Crescimento de Fibroblastos IGF-1 Hedgehog PI3K-AKT |
| title_short |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| title_full |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| title_fullStr |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| title_full_unstemmed |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| title_sort |
Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma |
| author |
Mendes, Jéssica Mariane Ferreira |
| author_facet |
Mendes, Jéssica Mariane Ferreira Valverde, Ludmila de Faro Vidal, Manuela Torres Andion Paredes, Bruno Diaz Coelho, Paulo Allahdadi, Kyan James Coletta, Ricardo Della Souza, Bruno Solano de Freitas Rocha, Clarissa Araújo Gurgel |
| author_role |
author |
| author2 |
Valverde, Ludmila de Faro Vidal, Manuela Torres Andion Paredes, Bruno Diaz Coelho, Paulo Allahdadi, Kyan James Coletta, Ricardo Della Souza, Bruno Solano de Freitas Rocha, Clarissa Araújo Gurgel |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Mendes, Jéssica Mariane Ferreira Valverde, Ludmila de Faro Vidal, Manuela Torres Andion Paredes, Bruno Diaz Coelho, Paulo Allahdadi, Kyan James Coletta, Ricardo Della Souza, Bruno Solano de Freitas Rocha, Clarissa Araújo Gurgel |
| dc.subject.other.pt_BR.fl_str_mv |
IGF-1 Ouriço Adenocarcinoma Fator 1 de Crescimento de Fibroblastos |
| topic |
IGF-1 Ouriço Adenocarcinoma Fator 1 de Crescimento de Fibroblastos IGF-1 Hedgehog PI3K-AKT |
| dc.subject.en.pt_BR.fl_str_mv |
IGF-1 Hedgehog PI3K-AKT |
| description |
CNPq, CAPES and FAPESB (grant number APP0006/2016). |
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2020 |
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2020-10-26T14:02:39Z |
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2020-10-26T14:02:39Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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MENDES, Jéssica Mariane Ferreira et al. Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences, 2020. |
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https://www.arca.fiocruz.br/handle/icict/44192 |
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1661-6596 |
| dc.identifier.doi.none.fl_str_mv |
10.3390/ijms21186487 |
| identifier_str_mv |
MENDES, Jéssica Mariane Ferreira et al. Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences, 2020. 1661-6596 10.3390/ijms21186487 |
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