da Silva, Sabrina Daniela and Marchi, Fabio Albuquerque and Su, Jie and Yang, Long and Valverde, Ludmila and Hier, Jessica and Bijian, Krikor and Hier, Michael and Mlynarek, Alex and Kowalski, Luiz Paulo and Alaoui-Jamali, Moulay A. (2021) Co-Overexpression of TWIST1-CSF1 Is a Common Event in Metastatic Oral Cancer and Drives Biologically Aggressive Phenotype. Cancers, 13 (1). p. 153. ISSN 2072-6694
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Abstract
Invasive oral squamous cell carcinoma (OSCC) is often ulcerated and heavily infiltrated by pro-inflammatory cells. We conducted a genome-wide profiling of tissues from OSCC patients (early versus advanced stages) with 10 years follow-up. Co-amplification and co-overexpression of TWIST1, a transcriptional activator of epithelial-mesenchymal-transition (EMT), and colony-stimulating factor-1 (CSF1), a major chemotactic agent for tumor-associated macrophages (TAMs), were observed in metastatic OSCC cases. The overexpression of these markers strongly predicted poor patient survival (log-rank test, p = 0.0035 and p = 0.0219). Protein analysis confirmed the enhanced expression of TWIST1 and CSF1 in metastatic tissues. In preclinical models using OSCC cell lines, macrophages, and an in vivo matrigel plug assay, we demonstrated that TWIST1 gene overexpression induces the activation of CSF1 while TWIST1 gene silencing down-regulates CSF1 preventing OSCC invasion. Furthermore, excessive macrophage activation and polarization was observed in co-culture system involving OSCC cells overexpressing TWIST1. In summary, this study provides insight into the cooperation between TWIST1 transcription factor and CSF1 to promote OSCC invasiveness and opens up the potential therapeutic utility of currently developed antibodies and small molecules targeting cancer-associated macrophages.
Item Type: | Article |
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Subjects: | Scholar Eprints > Materials Science |
Depositing User: | Managing Editor |
Date Deposited: | 23 Dec 2022 04:08 |
Last Modified: | 24 Aug 2024 13:57 |
URI: | http://repository.stmscientificarchives.com/id/eprint/239 |