Role of integrin β1 as a biomarker of sternness in head and neck squamous cell carcinoma

Objectives: Signaling between cancer stem cells (CSC) and their extracellular matrix has a crucial role in CSC progression and maintenance. However, mediators of this signaling pathway in head and neck squamous cell carcinoma (HNSCC) are largely unknown. Here, we explored whether integrin beta 1, which is one of the key regulators of the communication between cells and their microenvironment, affected the stemness of HNSCC cells. Materials and methods: We examined self-renewal capacity, chemoresistance, and xenograft tumorigenicity after knockdown of integrin beta 1 in primary HNSCC cells. In addition, we studied the role of focal adhesion kinase (FAK), an intracellular downstream molecule of integrin signaling, in influencing stemness of HNSCC. The relevance of Notch1 and integrin beta 1 interactions in HNSCC cells was also examined. Finally, immunohistochemical analysis was carried out to test whether the coexpression of integrin beta 1 and Notchl in the samples from HNSCC patients correlated with their survival. Results: Targeting integrin beta 1 in HNSCC cells inhibited self-renewal, chemoresistance, and in vivo tumor-forming capacity. Treatment with an inhibitor of FAK decreased self-renewal capacities and expression of various putative stem cell markers (Oct4, Sox2, and Nanog) in a dose-dependent manner. Moreover, knockdown of integrin beta 1 decreased the expression of Notchl and its target genes (Hey1 and Hes1). Notably, HNSCC patients demonstrating simultaneous expression of integrin beta 1 and Notchl in their tissue samples had significantly worse survival rate. Conclusion: Integrin beta 1/Notch1 axis has a significant role in the regulation of stemness in HNSCC.