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Activated Cdc42-associated kinase 1 (ACK1) is an oncogene in multiple cancers, but the underlying mechanisms of its oncogenic role remain unclear in non-small cell lung cancer (NSCLC). Herein, we comprehensively investigated the ACK1-regulated cell processes and downstream signaling pathways, as well as its prognostic value in NSCLC. We found that ACK1 gene amplification was associated with mRNA levels in The Cancer Genome Atlas (TCGA) lung cancer cohort. The Oncomine databases showed significantly elevated ACK1 levels in lung cancer. In vitro, an ACK1 inhibitor (dasatinib) increased the sensitivity of NSCLC cell lines to AKT or MEK inhibitors. RNA-sequencing results demonstrated that an ACK1 deficiency in A549 cells affected the MAPK, PI3K/AKT, and Wnt pathways. These results were validated by gene set enrichment analysis (GSEA) of data from 188 lung cancer cell lines. Using Cytoscape, we dissected 14 critical ACK1-regulated genes. The signature with the 14 genes and ACK1 could significantly dichotomize the TCGA lung cohort regarding overall survival. The prognostic accuracy of this signature was confirmed in five independent lung cancer cohorts and was further validated by a prognostic nomogram. Our study unveiled several downstream signaling pathways for ACK1, and the proposed signature may be a promising prognostic predictor for NSCLC.
Pubmed ID: 33495411
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Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsDatabase of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)
View all literature mentionsThe Biological Networks Gene Ontology tool (BiNGO) is an open-source Java tool to determine which Gene Ontology (GO) terms are significantly overrepresented in a set of genes. BiNGO can be used either on a list of genes, pasted as text, or interactively on subgraphs of biological networks visualized in Cytoscape. BiNGO maps the predominant functional themes of the tested gene set on the GO hierarchy, and takes advantage of Cytoscape''''s versatile visualization environment to produce an intuitive and customizable visual representation of the results. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible
View all literature mentionsWeb based gene set analysis toolkit designed for functional genomic, proteomic, and large-scale genetic studies from which large number of gene lists (e.g. differentially expressed gene sets, co-expressed gene sets etc) are continuously generated. WebGestalt incorporates information from different public resources and provides a way for biologists to make sense out of gene lists. This version of WebGestalt supports eight organisms, including human, mouse, rat, worm, fly, yeast, dog, and zebrafish.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsA unified data repository of the National Cancer Institute (NCI)'s Genomic Data Commons (GDC) that enables data sharing across cancer genomic studies in support of precision medicine. The GDC supports several cancer genome programs at the NCI Center for Cancer Genomics (CCG), including The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI). The GDC Data Portal provides a platform for efficiently querying and downloading high quality and complete data. The GDC also provides a GDC Data Transfer Tool and a GDC API for programmatic access.
View all literature mentionsA portal that provides visualization, analysis and download of large-scale cancer genomics data sets.
View all literature mentionsSoftware that clusters a given network based on topology to find densely connected regions. It can be used to find protein complexes and parts of pathways in protein-protein interaction networks or protein families in protein similarity networks.
View all literature mentionsWeb server for cancer and normal gene expression profiling and interactive analyses. Interactive web server for analyzing RNA sequencing expression data of tumors and normal samples from TCGA and GTEx projects, using standard processing pipeline. Provides customizable functions such as tumor or normal differential expression analysis, profiling according to cancer types or pathological stages, patient survival analysis, similar gene detection, correlation analysis and dimensionality reduction analysis.
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
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