Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF‐1/IGF‐1R signaling

Shi, Huancong; Fang, Winston; Liu, Minda; Fu, Deliang

doi:10.1002/ijc.30831

Cited by 34 publications

(34 citation statements)

References 45 publications

(54 reference statements)

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“…A variety of signaling pathways have been reported to be involved in the development and progression of PDAC including mitogen-activated protein kinase (MAPK) [8] and Notch [9] signaling pathways, growth factors such as epidermal growth factor (EGF) [8], fibroblast growth factor (FGF) [10] and insulin-like growth factor 1 (IGF-1) [11]. Based on these findings, scientists have uncovered various biological targets, and developed several corresponding targeted therapies [12, 13].…”

Section: Introductionmentioning

confidence: 99%

LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling

Xie

Zhang

Jin

et al. 2019

J Exp Clin Cancer Res

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Background The abnormal expression of leucine-rich-alpha-2-glycoprotein 1 (LRG-1) is reported to be associated with multiple malignancies, but its role in the progression of pancreatic ductal adenocarcinoma (PDAC) remains to be determined. Methods The expression of LRG-1 was assessed in PDAC tissues by RT-PCR, Western blot and immunohistochemistry. LRG-1-silenced or overexpressed cell lines were constructed using shRNA or LRG-1-overexpressing plasmids. EdU incorporation assay, Transwell invasion and wound-healing assays were performed to evaluate the proliferation, invasion and migration of PDAC cells. In addition, protein expression of the mitogen-activated protein kinase (MAPK) pathway was detected using Western blot. Finally, Co-immunoprecipitation assay was conducted in search of the potential interaction between LRG-1 and epidermal growth factor receptor (EGFR). Results The expression of LRG-1 in PDAC tissue was significantly higher than that in adjacent normal tissue, and high LRG-1 expression predicted poor survival and a late tumor stage. In addition, LRG-1 markedly promoted the viability, proliferation, migration and invasion of PDAC cells in vitro and facilitated tumor growth in vivo. More importantly, we revealed that these bioactivities of LRG-1 might result from its selective interaction with EGFR, which might further activate the p38/MAPK signaling pathways. Conclusion LRG-1 may prove to be a promising biomarker for predicting prognosis of PDAC patients. Inhibition of LRG-1 or its downstream pathway could be a potential therapeutic target for the treatment of PDAC.

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Section: Introductionmentioning

confidence: 99%

LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling

Xie

Zhang

Jin

et al. 2019

J Exp Clin Cancer Res

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“…And recent studies have con rmed that complement can promote tumor growth in mouse models (Markiewski and Lambris 2009). Moreover, in vivo and in vitro data show that tumor cells can activate complement (Bjorge, Hakulinen et al 2005, Corrales, Ajona et al 2012 and Shi et al (Shi, Fang et al 2017) reported that complement component 1, q subcomponent binding protein (C1QBP), in lipid rafts mediates liver metastasis of pancreatic cancer by regulating IGF-1 / IGF1R signaling. They reported that the expression of C1QBP in many human cancers is higher than that in normal tissues, including thyroid, lung, esophageal, gastric and colon cancer, and refer to previous reports that C1QBP mediates EGF induced chemotaxis and distant metastasis by activating receptor tyrosine kinase.…”

Section: Discussionmentioning

confidence: 99%

Identification of Significant Genes with poor prognosis in Liver Metastasis of Colorectal Cancer via Bioinformatical Analysis

Chen¹,

Liu²

2020

Preprint

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Background: Colorectal cancer (CRC) is a common malignant tumor in the world wild, and more than 50% patients have liver metastases. Purpose: The purpose of this study is to identify significant genes with poor outcome and the underlying mechanisms of CRC liver metastases. Methods: Gene expression profiles of GSE50760, GSE41568 and GSE14297 are available on website of GEO database. Differentially expressed genes (DEGs) between CRC liver metastases and primary tissues were picked out by GEO2R tool and Venn diagram software. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analyze Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and gene ontology (GO). Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Results: There were total of 147 consistently expressed genes in the three datasets, including 123 up-regulated genes and 24 down-regulated genes enriched in complement and coagulation cascades, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, prion diseases, chemical carcinogenesis, staphylococcus aureus infection and linoleic acid metabolism. Of PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, all 39 genes were selected. Moreover, for the analysis of CRC survival among those genes, Kaplan–Meier analysis was implemented and 4 (SERPING1 ITIH2 CDH2 APOE) of 39 genes had a significantly worse prognosis. Conclusion: we have identified four significant DEGs with poor prognosis in CRC liver metastases on the basis of integrated bioinformatical methods, which could be potential therapeutic targets for CRC patients with liver metastases.

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“…Mitochondrial C1qbp may also be responsible for the tumour-promoting property by increasing the energy for the growth of the cells and allowing glutamine addiction 42 . In addition, C1qbp may also contribute to metastasis 37 , for example, insulin-like growth factor induced the transition of C1qbp to the plasma membrane in pancreatic cancer cells, which promoted hepatic metastasis 43 . Inhibition of C1qbp was reported to suppress the growth of the tumour cells, which presents C1qbp as a potential drug target 34,43,44 .…”

Section: Introductionmentioning

confidence: 99%

Complement component 1q subcomponent binding protein in the brain of the rat

Barna

Dimén

Puska

et al. 2019

Sci Rep

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Complement component 1q subcomponent binding protein (C1qbp) is a multifunctional protein involved in immune response, energy homeostasis of cells as a plasma membrane receptor, and a nuclear, cytoplasmic or mitochondrial protein. Recent reports suggested its neuronal function, too, possibly in axon maintenance, synaptic function, and neuroplasticity. Therefore, we addressed to identify C1qbp in the rat brain using in situ hybridization histochemistry and immunolabelling at light and electron microscopic level. C1qbp has a topographical distribution in the brain established by the same pattern of C1qbp mRNA-expressing and protein-containing neurons with the highest abundance in the cerebral cortex, anterodorsal thalamic nucleus, hypothalamic paraventricular (PVN) and arcuate nuclei, spinal trigeminal nucleus. Double labelling of C1qbp with the neuronal marker NeuN, with the astrocyte marker S100, and the microglia marker Iba1 demonstrated the presence of C1qbp in neurons but not in glial cells in the normal brain, while C1qbp appeared in microglia following their activation induced by focal ischemic lesion. Only restricted neurons expressed C1qbp, for example, in the PVN, magnocellular neurons selectively contained C1qbp. Further double labelling by using the mitochondria marker Idh3a antibody suggested the mitochondrial localization of C1qbp in the brain, confirmed by correlated light and electron microscopy at 3 different brain regions. Post-embedding immunoelectron microscopy also suggested uneven C1qbp content of mitochondria in different brain areas but also heterogeneity within single neurons. These data suggest a specific function of C1qbp in the brain related to mitochondria, such as the regulation of local energy supply in neuronal cells.

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Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF‐1/IGF‐1R signaling

Cited by 34 publications

References 45 publications

LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling

LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling

Identification of Significant Genes with poor prognosis in Liver Metastasis of Colorectal Cancer via Bioinformatical Analysis

Complement component 1q subcomponent binding protein in the brain of the rat

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