SOX2 promotes a cancer stem cell-like phenotype and local spreading in oral squamous cell carcinoma

• Published in: PloS one Vol. 18; no. 12; p. e0293475
• Main Authors: Sacco, Alessandro, Battaglia, Anna Martina, Santamaria, Gianluca, Buffone, Caterina, Barone, Selene, Procopio, Anna, Lavecchia, Anna Maria, Aversa, Ilenia, Giorgio, Emanuele, Petriaggi, Lavinia, Cristofaro, Maria Giulia, Biamonte, Flavia, Giudice, Amerigo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-12-2023; Public Library of Science (PLoS)
• Subjects: Analysis; Biology and Life Sciences; Biomarkers; Cancer; CD44 antigen; Cell size; Chemotherapy; Cisplatin; Complications and side effects; CXCR4 protein; Development and progression; Diagnosis; Drug resistance; Gene expression; Genes; Genetic aspects; Genotype & phenotype; Head & neck cancer; Health aspects; Insulin-like growth factor I; Invasiveness; KLF4 protein; Lymph nodes; Lymphatic system; Medical prognosis; Medical research; Medicine and Health Sciences; Metastasis; Morphology; Mouth cancer; Mucosa; Oct-4 protein; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Patients; Phenotype; Phenotypes; Principal components analysis; Radiation therapy; Squamous cell carcinoma; Stem cells; Tumor cell lines; Tumors; Italy; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0293475

Emerging evidence shows that oral squamous cell carcinoma (OSCC) invasiveness can be attributed to a small subpopulation of cancer stem cells (CSCs) in the bulk of the tumor. However, the presence of CSCs in the OSCC close resection margins is still poorly unexplored. Here, we found that BMI1, CD44, SOX2, OCT4, UBE2C, CXCR4 CSCs marker genes are significantly upregulated, while IGF1-R, KLF4, ALDH1A1, CD133, FAM3C are downregulated in the tumor core vs healthy mucosa of 24 patients with OSCC. Among these, SOX2 appears also upregulated in the tumor close margin vs healthy mucosa and this significantly correlates with tumor size and lymph node compromise. In vitro analyses in CAL27 and SCC15 tongue squamous cell carcinoma cell lines, show that SOX2 transient knockdown i) promotes the mesenchymal-to-epithelial transition, ii) smooths the invasiveness, iii) attenuates the 3D tumor sphere-forming capacity, and iv) partially increases the sensitivity to cisplatin treatment. Overall, our study highlights that the OSCC close margins can retain CSC-specific markers. Notably, SOX2 may represent a useful CSCs marker to predict a more aggressive phenotype and a suitable target to prevent local invasiveness.