Deregulated expression of SOX11 has been shown to involve in the progression of various types of cancer. However, the role of SOX11 in head and neck cancer remains largely unknown. In this study, co-immunoprecipitation (Co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to identify the proteins that binds to SOX11 at significant higher levels in head and neck cancer cells compared to the normal human oral keratinocytes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many potential SOX11-binding partners were associated with protein synthesis, cell metabolism and cell-cell adhesion. One of the identified proteins, heat shock protein 90 alpha (HSP90α), was selected for further investigation. The binding of HSP90α with SOX11 in head and neck cancer cells was validated by Co-IP with Western blotting. In addition, HSP90α was found to be remarkably overexpressed in head and neck cancer cell lines when compared to the normal human oral keratinocytes, and knockdown of HSP90α inhibited the proliferation and invasion capacity of the cancer cells. Based on The Cancer Genome Atlas (TCGA) data analysis, HSP90AA1 gene was overexpressed in head and neck cancer tissues compared to normal controls and increased HSP90AA1 gene expression was positively associated with extracapsular spread and clinical stage. Head and neck cancer patients with higher HSP90AA1 expression had significantly poorer long term overall and disease free survival rates than those with lower HSP90AA1 expression. Collectively, our studies indicate that SOX11 binds to HSP90α, a highly over-expressed protein that may promote invasion and progression of head and neck cancer cells.

中文翻译：

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头颈癌细胞中SOX11结合蛋白的质谱分析表明SOX11与HSP90α的相互作用

SOX11的表达失调已被证明与各种癌症的进展有关。但是，SOX11在头颈癌中的作用仍然未知。在这项研究中，进行了共免疫沉淀（Co-IP）和液相色谱-串联质谱（LC-MS / MS），以鉴定与正常头颈部癌细胞相比，与SOX11结合的蛋白水平明显更高。人口腔角质形成细胞。基因本体论和《京都基因与基因组百科全书》（KEGG）途径分析表明，许多潜在的SOX11结合伴侣与蛋白质合成，细胞代谢和细胞粘附有关。选择一种鉴定出的蛋白，即热激蛋白90 alpha（HSP90α）进行进一步研究。通过Western blotting的Co-IP验证了HSP90α与SOX11在头颈癌细胞中的结合。另外，与正常人口腔角质形成细胞相比，发现HSP90α在头颈癌细胞系中显着过表达，并且敲低HSP90α抑制了癌细胞的增殖和侵袭能力。根据癌症基因组图谱（TCGA）数据分析，与正常对照组相比，HSP90AA1基因在头颈癌组织中过表达，并且HSP90AA1基因表达的增加与囊外扩散和临床分期呈正相关。HSP90AA1表达较高的头颈癌患者的长期总体生存率和无病生存率明显低于HSP90AA1表达较低的患者。总体而言，我们的研究表明SOX11与HSP90α结合，