Slug is a novel molecular target for head and neck squamous cell carcinoma stem-like cells

• Published in: Oral oncology 2020-12, Vol.111, p.104948-104948, Article 104948
• Main Authors: Moon, Jung Hwa, Lee, Sang Hyuk, Koo, Bon Seok, Kim, Jin Man, Huang, Songmei, Cho, Jae Hoon, Eun, Young Gyu, Shin, Hyang Ae, Lim, Young Chang
• Format: Article
• Language: English
• Subjects: Cancer stem cells; Head and neck cancer; Slug; Target therapy
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2020.104948

•There has been fewer definitive molecular indicators regulating stem cell traits of HNSCC.•Slug expression is closely associated with various stem cell traits, such as self-renewal, invasion, chemoresistance, and in vivo tumorigenecity of HNSCC cells.•Increased Slug expression worsens the prognosis of patients with HNSCC.•Slug is a novel molecular target for HNSCC stem-like cells. The acquisition of stem-like phenotype is partly attributed to the induction of epithelial-mesenchymal transition (EMT). Thus, the activation of factors involved in EMT can be linked to cancer stem cell genesis. However, the underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. Herein, we investigate whether slug, one of the major effectors of EMT, affects the stemness of HNSCC cells. We performed in vitro experiments to determine whether slug gene manipulation can influence the stemness phenotypes, including the capacity for self-renewal, expression of putative stemness markers, chemoresistance, and invasion in HNSCC cells. Further, we identified whether Slug knockout attenuates tumorigenicity of HNSCC cells in vivo. Finally, we examined whether prognosis of HNSCC patients after curative treatment may be affected by the level of slug expression. Overexpression of slug promoted self-renewal of HNSCC cells via activation of sphere formation, the expression of stem cell markers, and induction of chemoresistance to cisplatin. Also, slug overexpression increased the migration and invasion of HNSCC cells in vitro and was mainly observed during the invasion in HNSCC xenograft mouse model. By contrast, slug expression knockdown abrogated their self-renewal capacity, stemness-associated gene expression, and cisplatin chemoresistance. Furthermore, high levels of slug expression correlated with poor prognosis of patients with HNSCC. Inhibition of slug expression may represent a novel therapeutic strategy targeting HNSCC stem-like cells.