Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KLK6-related gene expression profile in FaDu cells

ABSTRACT: Epithelial-to-mesenchymal transition (EMT) is a dynamic process and critically contributes to treatment resistance, cancer cell dissemination and metastasis. Main objective of this study was to investigate the functional interaction between Kallikrein-related peptidase 6 (KLK6) and aldehyde dehydrogenase 1A (ALDH1A)-related retinoic acid (RA) signaling as recent studies reported their impact on molecular features resembling EMT in several malignancies, including head and neck squamous cell carcinoma (HNSCC). In HNSCC cell lines, we demonstrate that KLK6 is not only a downstream target of ALDH1A-related RA signaling, but also acts as an upstream regulator of ALDH1A3 expression. KLK6 and ALDH1A3 co-expression was confirmed in a mouse xenograft model and two independent HNSCC cohorts (HIPO-HNC and TCGA-HNC). KLK6 and ALDH1A3 co-expressed genes in HNSCC, which are also differentially expression in HNSCC cells with silenced KLK6 expression unraveled several subgroups of HNSCC patients with distinct histopathological and clinical features. In summary, our study highlights a new functional circuit with KLK6 and ALDH1A3 as key nodes and unraveled a gene expression signature, which predicts unfavorable prognosis in human papilloma virus (HPV)-negative HNSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122448 | GEO | 2021/11/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Involvement of kallikrein-related peptidase 6 in epithelial to mesenchymal transition induced by ΔNp63 downregulation in oral squamous cell carcinoma through activation of protease activated receptors

Project description:Recent studies showed epithelial-mesenchymal transition (EMT) is involved in cancer progression. Though we revealed that downregulation of ΔNp63 in oral squamous cell carcinoma (OSCC) induces EMT, the detailed molecular mechanisms remain to be elucidated. DNA microarray analyses were thus performed by using OSCC cell line overexpressing ΔNp63 to examine the genes associated with EMT. The results revealed that kallikrein related peptidase 6 (KLK6) was most upregulated in the OSCC cells overexpressing ΔNp63.

2018-04-01 | GSE90064 | GEO

Project description:KLK6-related gene expression profile in FaDu cells

| PRJNA505264 | ENA

KLK6 expression in skin induces PAR1-mediated psoriasiform dermatitis and inflammatory joint disease

Project description:Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptors (PAR)1 and PAR2. KLK6 levels are elevated in multiple inflammatory and autoimmune conditions, but no definitive role in pathogenesis has been established. Here, we show that skin-targeted overexpression of KLK6 causes generalized, severe psoriasiform dermatitis with spontaneous development of debilitating psoriatic arthritis-like joint disease. The psoriatic skin and joint phenotypes are reversed by normalization of skin KLK6 levels and attenuated following genetic elimination of PAR1 but not PAR2. Conservation of this regulatory pathway was confirmed in human psoriasis using vorapaxar, an FDA-approved PAR1 antagonist, on explanted lesional skin from psoriasis patients. Beyond defining a critical role for KLK6-PAR1 signaling in promoting psoriasis, our results demonstrate that KLK6-PAR1-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease. Further, we identify PAR1 as a promising cytokine-independent target in therapy of psoriasis and psoriatic arthritis.

2020-03-25 | GSE144312 | GEO

Global gene expression analysis of primary head and neck cancer cases

Project description:This study addressed the assumption that in addition to somatic mutations epigenetic silencing of cancer-related genes by promoter hyper-methylation is a common event in head and neck cancer. A multi-scale omics approach based on whole-exome sequencing, global DNA methylation and gene expression profiling data derived from tumor samples of the HIPO-HNC cohort was conducted and new findings were confirmed with data from TCGA-HNC. Results provide experimental evidence that the ryanodine receptor 2 (RYR2) exhibits variable promoter methylation and expression in both tumor samples and HNSCC cell lines. Moreover, immunohistochemical staining of tissue sections unraveled a gradual loss of RYR2 expression from normal mucosa via dysplastic lesions to cancer, and indicated that reduced RYR2 expression in adjacent tissue and precancer lesions might serve as a risk factor for unfavorable prognosis and upcoming malignant conversion.

2020-06-19 | GSE117973 | GEO

Validation and application of a novel KLK6 activity based probe (IMP2352)

Project description:Pancreatic cancer has the lowest survival rate of all common cancers due to late diagnosis and limited treatment options. Serine hydrolases are known to mediate cancer progression and metastasis through initiation of signaling cascades and cleavage of extracellular matrix proteins, and the kallikrein-related peptidase (KLK) family of secreted serine proteases have emerging roles in pancreatic ductal adenocarcinoma (PDAC). However, the lack of reliable activity-based probes (ABP) to profile KLK activity has hindered progress in validation of these enzymes as potential targets or biomarkers. Here, we developed potent and selective ABPs for KLK6 by using a positional scanning combinatorial substrate library and characterized their binding mode and interactions by X-ray crystallography. The optimized KLK6 probe IMP-2352 (kobs/I = 11,000 M-1 s-1) enabled selective detection of KLK6 activity in a variety of PDAC cell lines, and we observed that KLK6 inhibition reduced the invasiveness of PDAC cells that secrete active KLK6. KLK6 inhibitors were combined with N-terminomics to identify potential secreted protein substrates of KLK6 in PDAC cells, providing insights into KLK6-mediated invasion pathways. These novel KLK6 ABPs offer a new toolset to validate KLK6 and associated signaling partners as targets or biomarkers across a range of diseases.

2023-03-10 | PXD035111 | Pride

Gene expression profiling of African American vs European American HPV-negative oropharyngeal squamous cell carcinomas

Project description:Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25% are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. African American (AA) males have a higher incidence of HNC than any other racial/gender group, and a mortality rate almost three-fold that observed in European American (EA) males. Overall, AA patients tend to present with more HPV-negative OPC and have worse prognosis as compared to both HPV-positive and HPV-negative HNSCC in EA patients. Despite the unveiling of differential gene expression patterns, genetic and epigenetic profiles and the compilation of a mutational landscape along with preliminary TCGA data of HPV-related and unrelated HNC, the molecular determinants of the racial disparity in HNC are yet to be identified. This study aimed to compare the gene expression profiles of HPV-negative HNSCC from AA and EA patients, and determine their biological differences. ANALYSIS 2: Two-condition, on-color experiment: African American (AA) vs European American (EA) HPV-negative oropharyngeal squamous cell carcinomas. Biological replicates: 8 African American and 8 European American.

2014-03-05 | E-GEOD-55543 | biostudies-arrayexpress

Gene expression profiling of African American vs European American HPV-negative oropharyngeal squamous cell carcinomas

2014-03-05 | GSE55543 | GEO

CHD7 functions upstream of the retinoic acid synthetase ALDH1A3 to regulate inner ear development

Project description:CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an autosomal dominant condition characterized by variably penetrant abnormalities in craniofacial, cardiac, and neuronal tissues. The inner ear is uniquely sensitive to CHD7 levels and is the most commonly affected organ in individuals with CHARGE. Interestingly, up- or down-regulation of retinoic acid (RA) signaling during embryogenesis leads to developmental defects similar to those in CHARGE syndrome, suggesting CHD7 and RA share target genes or signaling pathways. Here, we report that CHD7 and retinoic acid receptor (RAR) do not directly interact, and that RA induces rapid neuronal differentiation of human SH-SY5Y neuroblastoma cells without affecting CHD7 levels. Instead, we provide evidence that CHD7 directly regulates expression of Aldh1a3, which encodes an RA synthetic enzyme, and that loss of Aldh1a3 partially rescues Chd7-mutant mouse inner ear defects, indicating that ALDH1A3 acts with CHD7 in a common genetic pathway to regulate inner ear development.

2020-08-30 | GSE103288 | GEO

The mRNA expression of FaDu-Ctrl, FaDu-Snail, FaDu-Snail2R cells

Project description:To screen the genes regulated by wt-Snail and non-acetylated Snail The successful development of cancer metastasis requires two major events: the reprogramming of cancer cells to increase their migration and tumor-initiation capabilities; and the remodeling of the tumor microenvironment to facilitate invasion and colonization of cancer cells. Epithelial-mesenchymal transition (EMT) is a crucial mechanism for reprogramming cancer cells to possess tumor initiation and migration capabilities1,2. However, the role of EMT in the interplay between tumor and host cells is largely unknown. The EMT regulator Snail is mainly known as a transcriptional repressor of the adhesion protein E-cadherin, whose repression is considered to be a key step in initiating metastasis3,4. We previously found that Snail can also act as an activator that induces the transcription of ERCC15 and IL86. Here we show that Snail is acetylated by CREB-binding protein (CBP) and that Snail and CBP co-occupy the promoters of target genes to activate transcription of the target genes. Furthermore, Snail activates the expression of a panel of cytokine genes, including TNFa (which forms a positive feedback loop with Snail to amplify the signal) and CCL2 and CCL5 (which facilitate the recruitment of macrophages by cancer cells). Our results demonstrate a novel function for Snail, providing new understanding of the recruitment of host cells to tumor sites during metastatic evolution. Establish stable transfectants of pCDH-Snail and pCDH-Snail2R in FaDu cells and analyze the mRNA expression level of by cDNA microarray. FaDu transfected with pCDH vector was used as a control experiment.

2014-08-16 | E-GEOD-58592 | biostudies-arrayexpress

Pretreatment microRNA expression impacting on epithelial to mesenchymal transition predicts intrinsic radiosensitivity in head and neck cancer cell lines and patients [FaDu]

Project description:Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex-vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biological processes that could be targeted to overcome intrinsic resistance. Experimental design: We analyzed both micro- and messenger RNA expression in a large panel of HNSCC cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of laryngeal cancer patients. Results: MiRs, mRNAs and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial to mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of laryngeal cancer patients. Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pre-treatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors.

2016-03-19 | GSE79371 | GEO