Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract and display few treatment options in advanced stages. Despite increased knowledge of HNSCC molecular biology, the identification of new players involved in triggering HNSCC recurrence and metastatic disease is needed. We uncover that G-protein-coupled receptor kinase-2 (GRK2) expression is reduced in undifferentiated, high-grade human HNSCC tumors, whereas its silencing in model human HNSCC cells is sufficient to trigger epithelial-to-mesenchymal transition (EMT) phenotypic features, an EMT-like transcriptional program and enhanced lymph node colonization from orthotopic tongue tumors in mice. Conversely, enhancing GRK2 expression counteracts mesenchymal cells traits by mechanisms involving phosphorylation and decreased functionality of the key EMT inducer Snail1. Our results suggest that GRK2 safeguards the epithelial phenotype, whereas its downregulation contributes to the activation of EMT programs in HNSCC.

中文翻译：

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G蛋白偶联受体激酶2可以保护头颈部鳞状细胞癌的上皮表型。

头颈部鳞状细胞癌（HNSCC）起源于上消化道的粘膜内层，在晚期阶段几乎没有治疗选择。尽管对HNSCC分子生物学的了解有所增加，但仍需要确定与触发HNSCC复发和转移性疾病有关的新参与者。我们发现在未分化的高级别人类HNSCC肿瘤中G蛋白偶联受体激酶2（GRK2）的表达降低，而其在模型人类HNSCC细胞中的沉默足以触发上皮向间质转化（EMT）的表型功能，EMT样转录程序和增强的小鼠原位舌头肿瘤的淋巴结定植。反过来，增强GRK2表达可通过涉及磷酸化和关键EMT诱导剂Snail1的功能降低的机制来抵消间充质细胞性状。我们的结果表明，GRK2可以保护上皮表型，而其下调则有助于激活HNSCC中的EMT程序。