Project description:Desmogleins are transmembrane cadherin proteins and obligate members of the desmosome, a cell-cell adhesion complex which connects adjacent cells and provides structural integrity to tissues. While Desmogleins are well-known for their importance in maintenance of cell-cell junctions, several studies have also highlighted their role in signaling crosstalk with cell-matrix adhesions and the extracellular matrix (ECM). We have recently shown that Desmoglein-2 (Dsg2) controls cell spreading on ECM substrates (fibronectin and collagen) and phosphorylation of focal adhesion proteins via Rap1 GTPase signaling. In our current study, we show that loss of Dsg2 in keratinocytes enhances the expression of ECM proteins and matrix metalloproteinases (MMPs), an effect that was not recapitulated upon loss of Desmocollin-2 (Dsc2) or loss of Dsg2 in other epithelial cell types. Signaling pathways well-known to control ECM function (TGF-B and Rho) were shown to have no effect on Dsg2-mediated changes in ECM and MMP gene expression, but an analysis of global transcriptome changes by RNA sequencing identified major changes in NF-kappaB (NF-KB)-mediated signaling in Dsg2-deficient cells. Interestingly, NF-KB (RelA) activation is elevated in Dsg2-deficient cells, and knockdown of RelA rescued both the enhanced expression of ECM/MMP genes and the enhanced migratory ability of Dsg2-deficient cells. Taken together, this study has identified an important link between Dsg2 and NF-KB signaling involved in controlling matrix production and remodeling, which has relevance for multiple processes in the epidermis such as wound healing and psoriasis.
Project description:Transcriptional profiling of human epidermoid carcinoma cell comparing control A431-P cells with highly invasive subline A431-III cells No treatmentt, A431-P cells vs. A431-III cells. A431-P cells are used as a reference to invstigate A431-III cells.
Project description:Transcriptional profiling of human epidermoid carcinoma cell comparing control A431-P cells with highly invasive subline A431-III cells
Project description:RNA sequencing of A431 cell line samples before and after gefitinib treatment, at 0, 2, 6 and 24 hours, was performed in order to characterize the cell line's early and late response to this drug, and to compare against proteomics (mass spectrometry) characterization of the cell line using the same setup. These data were used in Branca et al., HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics., Nat Methods. 2014 Jan;11(1):59-62 (doi: 10.1038/nmeth.2732).
Project description:Previously it has been shown that Id3 can act as an apoptosis-inducer gene in immortalized human keratinocytes. To further investigate the role of Id3 in the progression of skin cancer, the role of Id3 in A431 cells is investigated through ectopic induction of Id3. Microarray analysis is used to guide us the genes and pathways that are significantly altered after Id3 induction. 4 groups are included in this study, each with one sample. There are two cell lines: A431 cells stably transfected with Id3 or control vector. In each cell line, there are two conditions: induced and un-induced with tetracycline.
Project description:This study aims to investigate the transcriptional changes induced by overexpression of RNA-binding protein RBM3 in A431 human epidermoid carcinoma cells. Lentiviral transduction was used to stably overexpress RBM3 in A431 cells. Total RNA was extracted from RBM3 overexpressing cells and control cells, followed by RNA-seq library preparation and sequencing on Illumina platform. Differential gene expression analysis will be performed to identify RBM3 targets and regulatory networks.
Project description:TCF4 was silenced in cutaneous squamous cell carcinoma of A431 cells, and detected the mRNA profiles compared to the negative control and blank control.