ArticleMolecular & cellular proteomics : MCP2013
Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma.
Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- A hypoxia-related prognostic model predicts overall survival and treatment response in hepatocellular carcinoma.Bioscience reports · 2022Article
- The intercorrelation among CCT6A, CDC20, CCNB1, and PLK1 expressions and their clinical value in papillary thyroid carcinoma prognostication.Journal of clinical laboratory analysis · 2022Article
- Article
- miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma CellsFrontiers in molecular biosciences · 2020Article
- Phosphorylation of the multifunctional signal transducer B-cell adaptor protein (BCAP) promotes recruitment of multiple SH2/SH3 proteins including GRB2.The Journal of biological chemistry · 2019Article
- Increased Soluble CrkL in Serum of Breast Cancer Patients Is Associated with Advanced Disease.Cancers · 2019Article
- Overexpression of CrkL as a novel biomarker for poor prognosis in gastric cancer.Cancer biomarkers : section A of Disease markers · 2019Article
- The Methods Employed in Mass Spectrometric Analysis of Posttranslational Modifications (PTMs) and Protein-Protein Interactions (PPIs).Advances in experimental medicine and biology · 2019Review
- Biomarkers for hepatocellular carcinoma: What's new on the horizon?World journal of gastroenterology · 2018Article
- The long noncoding RNAThe Journal of biological chemistry · 2017Article
- Using knowledge-driven genomic interactions for multi-omics data analysis: metadimensional models for predicting clinical outcomes in ovarian carcinoma.Journal of the American Medical Informatics Association : JAMIA · 2017Article
- Visualization of Protein-protein Interaction in Nuclear and Cytoplasmic Fractions by Co-immunoprecipitation and In Situ Proximity Ligation Assay.Journal of visualized experiments : JoVE · 2017Article
- Multi-omic approaches for characterization of hepatocellular carcinoma.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2016Article
- Genomic mapping of pathways in endometrial adenocarcinoma and a gastrointestinal stromal tumor located in Meckel's diverticulum.Oncology letters · 2016Article
- CRKL oncogene is downregulated by p53 through miR-200s.Cancer science · 2015Article
- Article
- The association of Crk-like adapter protein with poor prognosis in glioma patients.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Knowledge-driven genomic interactions: an application in ovarian cancer.BioData mining · 2014Article
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Authors and funding
16 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKL-FLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition process. Our immunohistochemical analysis shows high expression levels of the CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples, and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.
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