sincalide and Laryngeal-Neoplasms

Lung squamous cell carcinoma (LSCC) is a prevalent and progressive subtype of lung cancer. This study aimed to substantiate the regulatory effect of the PAK2/SOX2/DEK axis on the LSCC development. LSCC tissues (n = 83) and adjacent normal tissues were collected and SOX2 expression was determined by qRT-PCR and Western blotting. Correlation between SOX2 expression and the prognosis of LSCC patients was then explored utilizing Kaplan-Meier analysis. Co-immunoprecipitation and glutathione-S-transferase pull-down assays were conducted to validate the binding of SOX2 to DEK. Gain- and loss- of function assays were then performed on LSCC cells, with CCK-8 and Transwell assays applied to detect the malignant behaviors of cells. A mouse xenograft model of LSCC was further established for in vivo validation. The expression levels of SOX2, PAK2 and DEK were up-regulated in LSCC tissues and cells. SOX2 overexpression was correlated with poor prognosis of LSCC patients. Knockdown of SOX2 weakened the viability and the migratory and invasive potential of LSCC cells. Further, PAK2 directly interacted with SOX2. PAK2 overexpression accelerated the malignant phenotypes of LSCC cells through interplay with SOX2. Moreover, SOX2 activated the expression of DEK, and silencing DEK attenuated the malignant behaviors of LSCC cells. In conclusion, PAK2 could bind to the transcription factor SOX2 and thus activate the expression of DEK, thereby driving the malignant phenotypes of LSCC cells both in vivo and in vitro.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Chromosomal Proteins, Non-Histone; Gene Expression Regulation, Neoplastic; Glutathione; Humans; Laryngeal Neoplasms; Lung; Lung Neoplasms; Mice; MicroRNAs; Oncogene Proteins; p21-Activated Kinases; Poly-ADP-Ribose Binding Proteins; Sincalide; SOXB1 Transcription Factors

To detect the expression of fibrinogen like protein-1 (FGL-1) in laryngeal cancer and evaluate its effect on tumor proliferation, metastasis, and antitumor immunity.. ELISA and immunohistochemistry were performed to detect FGL-1 expression in laryngeal cancer. The effects of FGL-1 knockdown on the proliferation, cell cycle progression, apoptosis, migration, and invasion of laryngeal cancer cells were evaluated by the CCK-8, colony formation, flow cytometry, Transwell migration, and western blot assays. We detected changes in tumorigenesis and drug response. FGL-1 was highly expressed in the plasma and tumor tissues of laryngeal cancer patients. FGL-1 knockdown suppressed the proliferation of TU-686 cells and inhibited the migration and invasion of laryngeal cancer by blocking epithelial-to-mesenchymal transition. Moreover, silencing FGL-1 inhibited tumorigenicity. We confirmed the high expression of FGL-1 in laryngeal cancer and identified FGL-1 as a potential marker for immunotherapy in laryngeal cancer.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Fibrinogen; Gene Expression Regulation, Neoplastic; Laryngeal Neoplasms; Mice; Sincalide

Yes-associated protein (YAP) plays a crucial role in tumour development and it is the main effector of the Hippo signalling pathway. However, the mechanism underlying YAP downregulation in laryngeal cancer is still unclear. In our previous study, we found that YAP, compared with adjacent tissues, was expressed higher in laryngeal cancer and was also closely associated with histological differentiation, TNM stage and poor prognosis.. In this study, we attempted to determine whether silenced YAP could downregulate human laryngeal carcinoma Hep-2 cells progression. YAP was downregulated in Hep-2 cells by shRNA, and the malignant ability of Hep-2 was assessed in vitro and in vivo.. In vitro, CCK-8, colony formation and wound healing assays showed that downregulation of YAP significantly reduced the rates of proliferation, migration, and invasion in Hep-2 cells. Downregulation of YAP distinctly induced G2/M cycle arrest and increased the rate of apoptosis. Accordingly, western blot assay suggested that the expression of DKK1, vimentin and β-catenin was significantly decreased after YAP downregulated treatment, thereby indicating that YAP mediated the EMT programme and the Wnt/β-catenin signalling pathway in carcinoma of the larynx. Furthermore, silencing of YAP suppressed Hep-2 cell tumourigenesis and metastasis in vivo.. In summary, our findings demonstrated the proliferation of YAP downregulation and the invasion of Hep-2 cells via downregulating the Wnt/β-catenin pathway in vitro and in vivo, suggesting that YAP may provide a potential therapeutic strategy for the treatment of laryngeal cancer.

Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis; beta Catenin; Cell Movement; Cell Proliferation; Down-Regulation; G2 Phase Cell Cycle Checkpoints; Gene Knockdown Techniques; Laryngeal Neoplasms; M Phase Cell Cycle Checkpoints; Male; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Neoplasm Staging; Phosphoproteins; RNA, Small Interfering; Sincalide; Transcription Factors; Tumor Stem Cell Assay; Vimentin; Wnt Signaling Pathway; Wound Healing; YAP-Signaling Proteins

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors, and the main cause of death is metastasis. Overexpression of aurora kinase A (AURKA) plays an important role in the metastasis of LSCC. However, the mechanism by which AURKA promotes the metastasis of LSCC is poorly understood. Recent accumulating evidence indicates that epithelial-mesenchymal transition (EMT) may be one of the mechanisms of tumor metastasis. In the present study, we studied whether AURKA may induce EMT to promote the metastasis of LSCC. CCK-8 and plate colony-formation assays were carried out to show that AURKA significantly promoted the proliferation of Hep2 cells. Immunofluorescence staining and western blotting showed that EMT-related proteins changed in a time-dependent manner along with the alteration of AURKA, with decreased expression of N-cadherin, vimentin and slug and increased expression of E-cadherin. Additionally, downregulation of the expression of AURKA inhibited FAK/PI3K pathway activity. Inhibition of the FAK/PI3K pathway caused less mesenchymal-like characteristics and reduced the mobility, migration and invasion of Hep2 cells. In conclusion, AURKA may induce EMT to promote metastasis via activation of the FAK/PI3K pathway in LSCC. Those regulatory factors may present new diagnostic biomarkers and potential therapeutic targets for LSCC.

Topics: Aurora Kinase A; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Epithelial-Mesenchymal Transition; Focal Adhesion Kinase 1; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Lymphatic Metastasis; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases; Signal Transduction; Sincalide; Snail Family Transcription Factors; Squamous Cell Carcinoma of Head and Neck; Vimentin