C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression

Oral squamous cell carcinoma (OSCC) represents 90% of malignant epithelial cancer that occurs in the oral cavity. The c-Myc factor is expressed in multiple types of cancer, comprising head and neck squamous cell carcinoma (HNSCC), where it plays a fundamental role in tumor prognosis and in the self-...

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Main Authors: Guya Diletta Marconi, Ylenia Della Rocca, Luigia Fonticoli, Francesco Melfi, Thangavelu Soundara Rajan, Simone Carradori, Jacopo Pizzicannella, Oriana Trubiani, Francesca Diomede
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/15/7/890
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author Guya Diletta Marconi
Ylenia Della Rocca
Luigia Fonticoli
Francesco Melfi
Thangavelu Soundara Rajan
Simone Carradori
Jacopo Pizzicannella
Oriana Trubiani
Francesca Diomede
author_facet Guya Diletta Marconi
Ylenia Della Rocca
Luigia Fonticoli
Francesco Melfi
Thangavelu Soundara Rajan
Simone Carradori
Jacopo Pizzicannella
Oriana Trubiani
Francesca Diomede
author_sort Guya Diletta Marconi
collection DOAJ
description Oral squamous cell carcinoma (OSCC) represents 90% of malignant epithelial cancer that occurs in the oral cavity. The c-Myc factor is expressed in multiple types of cancer, comprising head and neck squamous cell carcinoma (HNSCC), where it plays a fundamental role in tumor prognosis and in the self-renewal of tumor stem cells. However, the role of c-Myc in controlling OSCC cells is not well-known. The aim of the present study is the evaluation of the biological roles and regulatory mechanism of c-Myc in the pathogenesis of OSCC. Results indicated that c-Myc, c-Jun, Bcl-2, hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), ERK 1/2 and pERK1/2 were overexpressed in a cellular model of squamous cell carcinoma, Cal-27. Doxorubicin (Doxo), a common chemotherapeutic agent, inhibited cell invasion, hypoxia, angiogenesis and inflammation in a cellular model of Cal-27 cells as indicated by downregulation of MMP-9, VEGF, ERK 1/2 and pERK 1/2 as well as promoted apoptosis as evidenced by the downregulation of Bcl-2 protein. This work aimed at underlying the functional relevance of c-Myc in OSCC and the HIF-Myc collaboration by integrating the knowledge on this molecular link in an OSCC tumor microenvironment. The results obtained showed for the first time the vital role of c-Myc in Cal-27 in cell survival/proliferation and tumor growth as well as the negative regulatory effect of Doxo against c-Myc signaling pathway.
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spelling doaj.art-761a18b3886f43d18b2e8b59f53a25762023-11-30T21:40:47ZengMDPI AGPharmaceuticals1424-82472022-07-0115789010.3390/ph15070890C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer ProgressionGuya Diletta Marconi0Ylenia Della Rocca1Luigia Fonticoli2Francesco Melfi3Thangavelu Soundara Rajan4Simone Carradori5Jacopo Pizzicannella6Oriana Trubiani7Francesca Diomede8Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyDepartment of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Biotechnology, Karpagam Academy of Higher Education, Coimbatore 641021, IndiaDepartment of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalySs. Annunziata Hospital, ASL 02 Lanciano-Vasto-Chieti, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyOral squamous cell carcinoma (OSCC) represents 90% of malignant epithelial cancer that occurs in the oral cavity. The c-Myc factor is expressed in multiple types of cancer, comprising head and neck squamous cell carcinoma (HNSCC), where it plays a fundamental role in tumor prognosis and in the self-renewal of tumor stem cells. However, the role of c-Myc in controlling OSCC cells is not well-known. The aim of the present study is the evaluation of the biological roles and regulatory mechanism of c-Myc in the pathogenesis of OSCC. Results indicated that c-Myc, c-Jun, Bcl-2, hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), ERK 1/2 and pERK1/2 were overexpressed in a cellular model of squamous cell carcinoma, Cal-27. Doxorubicin (Doxo), a common chemotherapeutic agent, inhibited cell invasion, hypoxia, angiogenesis and inflammation in a cellular model of Cal-27 cells as indicated by downregulation of MMP-9, VEGF, ERK 1/2 and pERK 1/2 as well as promoted apoptosis as evidenced by the downregulation of Bcl-2 protein. This work aimed at underlying the functional relevance of c-Myc in OSCC and the HIF-Myc collaboration by integrating the knowledge on this molecular link in an OSCC tumor microenvironment. The results obtained showed for the first time the vital role of c-Myc in Cal-27 in cell survival/proliferation and tumor growth as well as the negative regulatory effect of Doxo against c-Myc signaling pathway.https://www.mdpi.com/1424-8247/15/7/890squamous cell carcinomadoxorubicintumor microenvironmentc-MycCal-27
spellingShingle Guya Diletta Marconi
Ylenia Della Rocca
Luigia Fonticoli
Francesco Melfi
Thangavelu Soundara Rajan
Simone Carradori
Jacopo Pizzicannella
Oriana Trubiani
Francesca Diomede
C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
Pharmaceuticals
squamous cell carcinoma
doxorubicin
tumor microenvironment
c-Myc
Cal-27
title C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
title_full C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
title_fullStr C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
title_full_unstemmed C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
title_short C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
title_sort c myc expression in oral squamous cell carcinoma molecular mechanisms in cell survival and cancer progression
topic squamous cell carcinoma
doxorubicin
tumor microenvironment
c-Myc
Cal-27
url https://www.mdpi.com/1424-8247/15/7/890
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