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Cancer stem cells (CSCs) may contribute to tumor initiation, distant metastasis and chemo-resistance. One of RNA-binding proteins, Quaking (QKI), was reported to be a tumor suppressor. Here we showed that reduced QKI levels were observed in many human oral cancer samples. Moreover further reduction of QKI expression in CSCs was detected compared with non-CSCs in oral cancer cell lines. Overexpressing QKI in oral cancer cells significantly reduced CSC sphere formation and stem cell-associated genes. In tumor implanting nude mice model, QKI significantly impeded tumor initiation rates, tumor sizes and lung metastasis rates. As a contrast, knocking down QKI enhanced the above effects. Among the putative CSC target genes, SOX2 expression was negatively affected by QKI, mechanism study revealed that QKI may directly regulate SOX2 expression via specific binding with its 3′UTR in a ciselement-dependent way. Loss of SOX2 even completely reversed the sphere forming ability in QKI knockdown cell line. Taken together, these data demonstrated that SOX2 is an important CSC regulator in oral cancer. QKI is a novel CSC inhibitor and impaired multiple oral CSC properties via partial repression of SOX2. Therefore, reduced expression of QKI may provide a novel diagnostic marker for oral cancer.

BackgroundDiscoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that is activated by fibrillar collagens. Although DDR2 contributes to the metastasis of some tumors, its role in head and neck squamous cell carcinoma (HNSCC) remains unknown. The aim of this study was to investigate the expression level, clinical and pathological significance, and biologic function of DDR2 in HNSCC.MethodsReal-time quantitative PCR, western blot, and immunohistochemical staining were employed to assess the expression levels of DDR2 in HNSCC specimens. Adenovirus-mediated overexpression of DDR2 was used to evaluate its consequences on cell proliferation, invasion, migration, and the process of hypoxia-induced epithelial-mesenchymal transition (EMT). Then nude mouse xenograft and tail vein metastasis models were utilized to validate the in vitro results.ResultsDDR2 was highly expressed in high grade HNSCC tissues and lowly expressed in low grade HNSCC tissues, but absent or rarely expressed in cancer-associated normal tissues. Both the frequency and expression intensity of DDR2 were significantly associated with tumor pathologic stage and lymph node metastasis. In vitro, DDR2 overexpression in HNSCC cells failed to alter cell proliferation but markedly accelerates cell invasion and migration as well as hypoxia-induced EMT. In vivo, elevated expression of DDR2 speeds up the metastasis of HNSCC cells to the lung.ConclusionDDR2 plays an important role in HNSCC metastasis, and might be a promising target for future therapies in this type of cancer.