Mass Spectrometric Analysis of SOX11-Binding Proteins in Head and Neck Cancer Cells Demonstrates the Interaction of SOX11 and HSP90α

Abstract

Deregulated expression of SOX11 has been shown to be involved in the progression of various types of cancer. However, the role of SOX11 in head and neck cancer remains largely unknown. In this study, coimmunoprecipitation (Co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to identify the proteins that bind to SOX11 at significantly higher levels in head and neck cancer cells than in normal human oral keratinocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses 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 its level in normal human oral keratinocytes, and knockdown of HSP90α inhibited the proliferation and invasion capacity of these cancer cells. On the basis of 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 overexpressed protein that may promote invasion and progression of head and neck cancer cells.

Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging

“…The prognostic protein UBR4, not included by STRING, is also associated with EGFR (18) and was manually added to the network. Similarly SOX11, reported to interact with GART (19), was manually added to the network (Figure 6). Thus, after manual curation, of the 9 discovered proteins with potential prognostic utility in TNBC, all except the two proteins without known functions (CCDC24 and ZSWIM8) could be functionally linked in a network centered on EGFR.…”

“…SOX11, described by others as a marker of poor prognosis in basal-like breast cancer (48)—although another study unstratified for subtype did not show this effect (49)—has been proposed as a therapeutic target in breast (48) and other (50) cancers. As noted above, SOX11 can be included in the STRING network through its interaction, identified by coimmunoprecipitation and LC-MS/MS (19) with the purine biosynthetic protein GART. Thus, of the 9 proteins we have identified by MALDI MSI as having potential prognostic value in TNBC, only the two without known function (CCDC24 and ZSWIM8) were unable to be included in a single interaction network.…”

Exosome‑delivered TRPP2 siRNA inhibits the epithelial‑mesenchymal transition of FaDu cells

“…Head and neck cancer (HNC) is one of the most common malignant neoplasms observed worldwide (1). Although early detection and therapeutic strategies for HNC, including radiotherapy, chemotherapy, immunotherapy and surgery, have substantially improved, the outcomes for patients with HNC remain poor, with an overall 5-year survival rate of only 50% (2,3). Therefore, it is important to find novel treatment strategies for HNC.…”

SOX Genes and Cancer

“…A biochemical interaction is validated between SOX11 and HSP90α through the co-immunoprecipitation with Western blot analysis. In addition, we have found that downregulation of HSP90α inhibits the malignant phenotypes of HNC cells and HSP90α upregulation is significantly associated with worse clinical outcome of HNC, suggesting HSP90α might serve as a potential prognostic biomarker and therapeutic target for HNC [84].…”