Liprin-α1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton

BackgroundPPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-α1 encoded by PPF1A1 contributes to the adhesive and invasive structures of cytoskeletal elements and is located at the invadosomes in cancer cells. However, the precise mechanism of liprin-α1 function in cancer progression has remained elusive.MethodsInvasion regulating activity of liprin-α1 was examined by analyzing the functions of squamous cell carcinoma of head and neck (HNSCC) cell lines in three-dimensional collagen I after RNAi mediated gene knockdown. Transcriptome profiling and Gene Set Enrichment Analysis from HNSCC and breast cancer cells were used to identify expression changes relevant to specific cellular localizations, biological processes and signaling pathways after PPFIA1knockdown. The significance of the results was assessed by relevant statistical methods (Wald and Benjamini-Hochberg). Localization of proteins associated to liprin-α1 was studied by immunofluorescence in 2D and 3D conditions. The association of PPFIA1 amplification to HNSCC patient survival was explored using The Cancer Genome Atlas data.ResultsIn this study, we show that liprin-α1 regulates biological processes related to membrane microdomains in breast carcinoma, as well as protein trafficking, cell-cell and cell-substrate contacts in HNSCC cell lines cultured in three-dimensional matrix. Importantly, we show that in all these cancer cells liprin-α1 knockdown leads to the upregulation of transmembrane protein CD82, which is a suppressor of metastasis in several solid tumors.ConclusionsOur results provide novel information regarding the function of liprin-α1 in biological processes essential in cancer progression. The results reveal liprin-α1 as a novel regulator of CD82, linking liprin-α1 to the cancer cell invasion and metastasis pathways.</div

Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies

Background: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). Results/methodology: pAKT was induced by hypoxia (0.5% O2) in a part of HNSCC (3/4) and squamous (2/3) and adenocarcinoma (1/3) NSCLS lines. AKT-inhibitor MK-2206 reduced hypoxic HIF-1 signaling in most HNSCC cell lines. This reduction did not correlate with hypoxic induction of pAKT or with sensitivity to MK-2206 under hypoxia. Patient biopsies revealed a hypoxia-induced expression pattern of pAKT in HNSCC (n = 16), which was not observed in squamous cell (n = 34) or adenocarcinoma (n = 41) NSCLC. Conclusion: The interaction between hypoxia, HIF-1 and AKT signaling varies between tumor types and histologies, which could significantly affect response to targeted therapies.</p

Modelling of homogeneously catalyzed hemicelluloses hydrolysis in a laminar-flow reactor

Hydrolysis of hemicelluloses with acid catalysts yield different sugar monomers and oligomers, depending on the substrate as well as the process design. The hydrolysis kinetics are typically rather slow, which leads to requirements of long residence times, i.e. slow flow rates, in order to achieve adequate conversion. Hydrolysis experiments of two different polysaccharides – o-acetylgalactoglucomannan (GGM) and inulin - were conducted in an isothermal tubular continuous reactor in laboratory scale, working in the laminar flow regime. A dynamic mass balance-based reactor model was developed, including convection and molecular diffusion in axial and radial directions, as well as the self-accelerating kinetics of the reaction. The model gave a very satisfactory description of the experimental data. The behavior of the laminar flow reactor in the hemicellulose hydrolysis was further illustrated by numerical simulations

Hypoxic regulation of the PERK/ATF4/LAMP3-arm of the unfolded protein response in head and neck squamous cell carcinoma

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The presence of human papillomavirus (HPV) in placenta and/or cord blood might result in Th2 polarization

Experimental cancer immunology and therap