CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway

Ding, Xusheng; Huang, Run; Zhong, Yiming; Cui, Na; Wang, Yifei; Weng, Junyong; Chen, Li; Zang, Mingde

doi:10.1016/j.biopha.2019.109742

Cited by 49 publications

(47 citation statements)

References 31 publications

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“…Furthermore, it was found that inhibition of HIF-1 α expression and inhibition of CXCL12/CXCR4 signals all alleviate tumor cell migration and invasion. Therefore, CTHRC1 can participate in tumor cell migration and invasion through HIF-1 α /CXCR4 signals in GC [ 132 ]. In short, CTHRC1 can affect the expression of HIF-1 α , which is not only related to lymphangiogenesis but also closely related to tumor progression and invasion.…”

Section: Signaling Pathways Mediated By Cthrc1 Involved In the Promentioning

confidence: 99%

The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis

Mei

Zhu

Zhang

et al. 2020

Mediators of Inflammation

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Collagen triple helix repeat containing-1 (CTHRC1) has been identified as cancer-related protein. CTHRC1 expresses mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels and promotes cell migration and tissue repair in response to injury. CTHRC1 plays a pivotal role in some pathophysiological processes, including increasing bone mass, preventing myelination, and reversing collagen synthesis in many tumor cells. The ascended expression of CTHRC1 is related to tumorigenesis, proliferation, invasion, and metastasis in various human malignancies, including gastric cancer, pancreatic cancer, hepatocellular carcinoma, keloid, breast cancer, colorectal cancer, epithelial ovarian cancer, esophageal squamous cell carcinoma, cervical cancer, non-small-cell lung carcinoma, and melanoma. And molecules that regulate the expression of CTHRC1 include miRNAs, lncRNAs, WAIF1, and DPAGT1. Many reports have pointed that CTHRC1 could exert different effects through several signaling pathways such as TGF-β, Wnt, integrin β/FAK, Src/FAK, MEK/ERK, PI3K/AKT/ERK, HIF-1α, and PKC-δ/ERK signaling pathways. As a participant in tissue remodeling or immune response, CTHRC1 may promote early-stage cancer. Several recent studies have identified CTHRC1 as an effectual prognostic biomarker for predicting tumor recurrence or metastasis. It is worth noting that CTHRC1 has different cellular localization and mechanisms of action in different cells and different microenvironments. In this article, we focus on the advances in the signaling pathways mediated by CTHRC1 in tumors.

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Section: Signaling Pathways Mediated By Cthrc1 Involved In the Promentioning

confidence: 99%

The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis

Mei

Zhu

Zhang

et al. 2020

Mediators of Inflammation

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“…All of the above genes are associated with the occurrence and development of GC in different degrees, which also proves the reliability of our analysis results. BGN, NOX4, SPARC, HEYL, SPP1, CTHRC1, SFRP4, FBXO32, KIF4A, MMP9, TIMP1 were related to the proliferation, invasion, prognosis, and recurrence of GC in different level and validated in many kind of tumors [25][26][27][28][29][30][31][32][33][34][35][36][37]. The key gene GPX3 is downregulation in GC cell lines and samples because of abnormal promoter methylation, and related to lymph node metastasis [38].…”

Section: Discussionmentioning

confidence: 95%

High expression of TREM2 promotes EMT via the PI3K/AKT pathway in gastric cancer: bioinformatics analysis and experimental verification

Hou

Yuan

et al. 2021

J. Cancer

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Background: To date, the pathogenesis of gastric cancer (GC) remains unclear. We combined public database resources and bioinformatics analysis methods, explored some novel genes and verified the experiments to further understand the pathogenesis of GC and to provide a promising target for anti-tumor therapy. Methods: We downloaded the chip data related to GC from the Gene Expression Omnibus (GEO) database, extracted differentially expressed genes (DEGs), and then determined the key genes in the development of GC via PPI networks and model analysis. Functional annotation via GO and KEGG enrichment of DEGs was used to understand the latent roles of DEGs. The expression of the triggering receptor expressed on myeloid cells 2 (TREM2) gene in GC cell lines was verified via RT-PCR and western blotting. Moreover, the CCK-8, wound healing assay, and transwell migration and invasion assays were used to understand the changes in the proliferation, migration, and invasion abilities of GC cells after silencing TREM2. Western blotting verified the interaction between TREM2 and PI3K predict of the string website, as well as the effect of TREM2 on EMT. Finally, a lung metastasis model was used to explore the relationship between TREM2 and metastasis. Results: Our study identified 16 key genes, namely BGN,

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“…The HIF-1 signaling pathway is involved in tumor growth, proliferation, and migration ( Tian et al, 2015 ; Macklin et al, 2017 ). The HIF-1α signaling pathway mediates the promotion of CThrC1 in the migration and invasion of gastric cancer cells ( Ding et al, 2020 ). The cell cycle is also important for the occurrence and development of many cancers, and it is an important mechanism of cell growth, development, metabolism, and regeneration ( Evan and Vousden, 2001 ; Icard et al, 2019 ), which is closely related to the degree of tumor differentiation, invasion area, vascular invasion, and lymphatic metastasis ( Machlowska et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics

et al. 2021

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BackgroundGastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.MethodsFerroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).ResultsA ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.ConclusionOur prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.

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CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway

Cited by 49 publications

References 31 publications

The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis

The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis

High expression of TREM2 promotes EMT via the PI3K/AKT pathway in gastric cancer: bioinformatics analysis and experimental verification

Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics

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