Department of Oral and Cranio-Maxillofacial Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Head Neck. 2018 Dec;40(12):2685-2694. doi: 10.1002/hed.25515. Epub 2018 Nov 20.
Cortactin (CTTN) is located on chromosome 11q13 and is associated with invasiveness in various cancer entities. CTTN protein expression could be a prognosticator of oral squamous cell carcinoma (OSCC) in terms of recurrence and survival.
CTTN-dependent invasion was performed using migration assay in human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) cells. Cortactin protein analysis in tissue microarrays was used for correlation with clinical parameters, as well as for survival analysis. Gene expression profiling in HNSCC cells was performed to unreveal CTTN signaling.
Knockdown of CTTN in HNSCC cells showed less invasion in vitro. Gene expression profiling showed various deregulated genes known to be involved in progression. We confirmed the link between CTTN overexpression and progression in a large clinical cohort. High expression was associated with worse overall and progression-free survival.
We propose CTTN for managing OSCC in terms of adjuvant therapy and aftercare. Furthermore, our study reveals new potential targets in CTTN signaling for individualized OSCC therapy.
Cortactin（CTTN）位于 11q13 染色体上，与多种癌症实体的侵袭性有关。CTTN 蛋白表达可能是口腔鳞状细胞癌（OSCC）复发和生存的预后因子。
采用人乳头瘤病毒阴性的头颈部鳞状细胞癌（HNSCC）细胞中的迁移试验进行 CTTN 依赖性侵袭。利用组织微阵列进行 CTTN 蛋白分析，以与临床参数相关联，并进行生存分析。对 HNSCC 细胞进行基因表达谱分析，以揭示 CTTN 信号通路。
在 HNSCC 细胞中敲低 CTTN 显示体外侵袭性降低。基因表达谱分析显示了各种已知参与进展的失调基因。我们在一个大型临床队列中证实了 CTTN 过表达与进展之间的联系。高表达与总生存率和无进展生存率降低相关。
我们提出 CTTN 可用于管理 OSCC 的辅助治疗和后续治疗。此外，我们的研究揭示了 CTTN 信号通路中用于个体化 OSCC 治疗的新的潜在靶点。
