Department of Otorhinolaryngology - Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
Department of Otolaryngology - Head and Neck Surgery, Hallym University College of Medicine, Seoul, Republic of Korea.
Oral Oncol. 2019 Sep;96:34-41. doi: 10.1016/j.oraloncology.2019.07.001. Epub 2019 Jul 4.
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.
癌细胞干细胞（CSC）与其细胞外基质之间的信号传递在 CSC 的进展和维持中起着关键作用。然而，头颈部鳞状细胞癌（HNSCC）中这种信号通路的介质在很大程度上尚不清楚。在这里，我们探讨了整合素β1是否会影响 HNSCC 细胞的干性，整合素β1是细胞与其微环境之间通讯的关键调节剂之一。
我们在原代 HNSCC 细胞中敲低整合素β1后，检测了自我更新能力、化学抗性和异种移植肿瘤形成能力。此外，我们研究了整合素信号的细胞内下游分子粘着斑激酶（FAK）在影响 HNSCC 细胞干性中的作用。还研究了 Notch1 和整合素β1相互作用在 HNSCC 细胞中的相关性。最后，进行免疫组织化学分析以检测 HNSCC 患者样本中整合素β1和 Notch1的共表达是否与其生存相关。
靶向 HNSCC 细胞中的整合素β1抑制了自我更新、化学抗性和体内肿瘤形成能力。FAK 抑制剂的处理以剂量依赖性方式降低了自我更新能力和各种假定的干细胞标志物（Oct4、Sox2 和 Nanog）的表达。此外，敲低整合素β1降低了 Notch1及其靶基因（Hey1 和 Hes1）的表达。值得注意的是，在组织样本中同时表达整合素β1和 Notch1的 HNSCC 患者的生存率显著降低。
整合素β1/Notch1 轴在调节 HNSCC 中的干性方面起着重要作用。
