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Co-Overexpression of TWIST1-CSF1 is a Common Event in Metastatic Oral Cancer and Drives Biologically Aggressive Phenotype
- Source :
- Cancers, Vol 13, Iss 153, p 153 (2021), Cancers, Volume 13, Issue 1
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Simple Summary There is clinical evidence that ulcerated and inflammatory cell-infiltrated oral cancer is frequently associated with early metastases. Our results from genomic screening in patients with metastatic oral cancer identified specific changes in genes that regulate macrophage chemotaxis and drive tumor progression. This opens up potential therapeutic opportunities toward personalized medicine tailored to manage patients with advanced disease. 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.
- Subjects :
- 0301 basic medicine
Cancer Research
animal structures
TWIST1
lcsh:RC254-282
Article
Metastasis
genomic
03 medical and health sciences
0302 clinical medicine
In vivo
CSF1
medicine
Gene silencing
Macrophage
metastasis
Transcription factor
biology
business.industry
tumor-associated macrophages
EMT
Cancer
tumor invasion
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
oral squamous cell carcinoma
stomatognathic diseases
030104 developmental biology
Oncology
Cell culture
030220 oncology & carcinogenesis
biology.protein
Cancer research
Antibody
business
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 13
- Issue :
- 153
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....1cf9ff50c225b825cf6a0300911d3a31