Details

Autor(en) / Beteiligte

• Moon, Jung Hwa
• Rho, Young Soo
• Lee, Sang Hyuk
• Koo, Bon Seok
• Lee, Hyun Joo
• Do, Sung Im
• Cho, Jae Hoon
• Eun, Young Gyu
• Park, Min Woo
• Shin, Hyang Ae
• Lim, Young Chang

Titel

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

Ist Teil von

• Oral oncology, 2019-09, Vol.96, p.34-41

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •Suppression of integrin β1 decreases stemness of HNSCC cells in vitro and in vivo.•FAK is the main mediator of the integrin β1 signaling pathway affecting stemness of HNSCC cells.•Co-expression of integrin β1 and Notch1 is a valuable prognostic indicator for patients of HNSCC.•Integrin β1 has a significant role in the regulation of stemness in HNSCC. 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 β1, which is one of the key regulators of the communication between cells and their microenvironment, affected the stemness of HNSCC cells. We examined self-renewal capacity, chemoresistance, and xenograft tumorigenicity after knockdown of integrin β1 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 β1 interactions in HNSCC cells was also examined. Finally, immunohistochemical analysis was carried out to test whether the coexpression of integrin β1 and Notch1 in the samples from HNSCC patients correlated with their survival. Targeting integrin β1 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 β1 decreased the expression of Notch1 and its target genes (Hey1 and Hes1). Notably, HNSCC patients demonstrating simultaneous expression of integrin β1 and Notch1 in their tissue samples had significantly worse survival rate. Integrin β1/Notch1 axis has a significant role in the regulation of stemness in HNSCC.