ArticleBMC cancer2015
The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Somatostatin Receptor 2 Overexpression in Hepatocellular Carcinoma: Implications for Cancer Biology and Therapeutic Applications.Current oncology (Toronto, Ont.) · 2025Article
- Role of TInternational journal of molecular sciences · 2025Article
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
- Insulin-like growth factor binding protein-2 and glucose-regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH-wildtype glioblastoma patients.Cancer medicine · 2023Article
- CX3CL1 induces cell migration and invasion through ICAM-1 expression in oral squamous cell carcinoma cells.Journal of cellular and molecular medicine · 2023Article
- Inflammatory bowel disease increases the risk of hepatobiliary pancreatic cancer: A two-sample Mendelian randomization analysis of European and East Asian populations.Cancer medicine · 2023Article
- Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence.Cancer metastasis reviews · 2023Review
- Article
- Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease.Biomedicines · 2021Article
- HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway.Oncogene · 2021Article
- GALNT6 promotes breast cancer metastasis by increasing mucin-type O-glycosylation of α2M.Aging · 2020Article
- Review
- Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma.BMC cancer · 2020Article
- Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway.Oxidative medicine and cellular longevity · 2019Article
- Glucose-Regulated Protein 78 Signaling Regulates Hypoxia-Induced Epithelial-Mesenchymal Transition in A549 Cells.Frontiers in oncology · 2019Article
- Sevoflurane relieves hepatic ischemia-reperfusion injury by inhibiting the expression of Grp78.Bioscience reports · 2018Article
- miR‑495 enhances the efficacy of radiotherapy by targeting GRP78 to regulate EMT in nasopharyngeal carcinoma cells.Oncology reports · 2018Article
- Up-regulation of CTD-2547G23.4 in hepatocellular carcinoma tissues and its prospective molecular regulatory mechanism: a novel qRT-PCR and bioinformatics analysis study.Cancer cell international · 2018Article
- Article
- Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma.Scientific reports · 2017Article
Corrections and comments
- Retracted
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmerging data have suggested that cell surface GRP78 is a multifunctional receptor and has been linked to proliferative and antiapoptotic signaling cascades. Activated α2-macroglobin (α2M*) is a natural circulating ligand of cell surface GRP78. Association of cell surface GRP78 with α2M* is involved in the regulation of cell proliferation, survival and apoptosis in human cancers.
methodsThe invasion and metastasis of HCC cells were examined using transwell and wound healing assay; Cell surface expression of GRP78 was detected by in cell western assay. Translocation of GRP78 from cytosol to cell surface was observed by transfection of GRP78-EGFP plus TRIRC-WGA staining. The levels of Src, phosphor-Src, FAK, phospho-FAK, EGFR, phospho-EGFR, phospho-Cortactin, phospho-Paxillin were determined by western blot. Cell surface expression of GRP78 in HCC tissue samples was observed by immunofluorescence. The distribution of Paxillin and Cortactin in HCC cells was also observed by immunofluorescence. The interaction between GRP78 and Src were detected by far-western blot, co-immunoprecipitation and GST pulldown. GRP78 mRNA was detected by RT-PCR.
resultsIn the current study, we showed that association of cell surface GRP78 with α2M* stimulated the invasion and metastasis of HCC. Cell surface GRP78 could interact directly with c-Src, promoted the phosphorylation of c-Src at Y416. Inhibition of the tyrosine kinase activity of c-Src with PP2 reverted the stimulatory effect caused by association of cell surface GRP78 with α2M*. Moreover, association of cell surface GRP78 with α2M* facilitates the interaction between EGFR and c-Src and consequently phosphorylated EGFR at Y1101 and Y845, promoting the invasion and metastasis of HCCs. However, inhibition of the tyrosine kinase of c-Src do not affect the interaction between EGFR and Src.
conclusionc-Src plays a critical role in the invasion and metastasis of HCC induced by association of cell surface GRP78 with α2M*. Cell surface GRP78 directly binds and phosphorylates c-Src. As a consequence, c-Src phosphorylated EGFR, promoting the invasion and metastasis of HCCs.
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