| Summary: | 碩士 === 國立陽明大學 === 口腔生物研究所 === 98 === Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs) from HNSCC. However, the molecular mechanisms by which to govern the characteristics in HN-CICs remain unclear.GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not elucidated. Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by proteomic analysis. Subsequently, flow cytometry cell sorting was applied to purify memGRP78+ cells for evaluating CICs properties.
Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells, and stemness genes expression of HN-CICs. Additionally, down-regulation GRP78 of enhanced the differentiation and apoptotic capability of HN-CICs. Importantly, targeting GRP78 lessened in vitro and in vivo tumorigenicity of HN-CICs. Clinically, GRP78 was positively correlated with Nanog, and co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients.
In summary, targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs and memGRP78 could be a novel surface marker for isolation HN-CICs.
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