CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1

Yang, Tao; Wang, Huibing; Li, Meng; Yang, Linqi; Han, Yu; Liu, Chao; Zhang, Baowen; Ming-fa, WU; Wang, Gang; Zhang, Zhenya; Zhang, Wenqi; Huang, Jianming; Zhang, Huaxing; Cao, Ting; Chen, Pingping; Zhang, Wei

doi:10.7150/ijbs.53657

Cited by 11 publications

(11 citation statements)

References 35 publications

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“…CEACAM6 is a human tumor marker found in excess in colon tumors. Moreover, B2 phylogroup E. coli strains associated with Crohn’s disease intensify the expression of CEACAM6 receptors in gut epithelial cells ( Jantscheff et al., 2003 ; Ferlizza et al., 2020 ; Yang et al., 2021 ). Most AIEC isolates belong to phylogroups B2 (54.2%) and D (29.2%).…”

Section: Discussionmentioning

confidence: 99%

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran

Dolatabadi

Fazeli

Karbasizade

et al. 2022

Front. Cell. Infect. Microbiol.

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There is increasing evidence showing that microbial dysbiosis impacts the health and cancer risk of the host. An association between adherent–invasive Escherichia coli (AIEC) and colorectal cancer (CRC) has been revealed. Cyclomodulins (CMs) have been receiving increasing attention for carcinogenic changes. In this study, the incidence and features of intracellular AIEC and cyclomodulin-encoding genes were investigated and the phylogenetic grouping and genetic relatedness were evaluated. E. coli strains were isolated from the colorectal biopsies. Adhesion and invasion assays and intramacrophage cell survival test were performed to separate the AIEC isolates. Virulence genotyping for the genes htrA, dsbA, chuA, and lpfA and the cyclomodulin toxins was also conducted. In addition, phylogenetic grouping of the isolates was determined. Subsequently, repetitive element sequence-based PCR (rep-PCR) fingerprinting was performed. A total of 24 AIEC pathovars were isolated from 150 patients. The prevalence rates of htr, dsbA, and lpfA were 70.83% and that of chuA was 91.66%. The frequencies of the cyclomodulin toxins were as follows: cnf1, 29.2%; cnf2, 25%; colibactin, 29.2%; and cdt, 4.2%; cif was not found. Among the AIEC isolates, 4.2%, 4.2%, 54.2%, 29.2%, and 8.3% with phylotypes A or C, B1, B2, D, and E were identified, respectively. Left-sided colon carcinoma and adenocarcinoma T≥1 stage (CRC2) were colonized by B2 phylogroup AIEC-producing CMs more often than the samples from the other groups. Close genetic relatedness was observed in AIEC isolates with rep-PCR.

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Section: Discussionmentioning

confidence: 99%

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran

Dolatabadi

Fazeli

Karbasizade

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Many pathways are associated with the pathogenesis of CD. Signaling pathway include immune system [69], neutrophil degranulation [114], GDF15 [115], IL1RN [116] STAT1 [117], SLAMF7 [105], CYP27B1 [118], NETO2 [119], TFPI2 [120], ZC3H12A [121], MMP1 [122], CSF3 [123], SOCS3 [124], TLR8 [125], HTRA3 [126], CEBPB (CCAAT enhancer binding protein beta) [127], CD55 [128], CXCR2 [129], CCL28 [130], CBR3 [131], CCL3 [132], FCGR2A [48], ACSL1 [133], CCL2 [134], SOD2 [135] [150], CCR2 [151], VWF (von Willebrand factor) [152], SLC7A11 [153], NOD2 [154], DMBT1 [155], IL20RA [156], TYMP (thymidine phosphorylase) [144], S100P [157], PDPN (podoplanin) [158], ADAMTS1 [159], ATF3 [160], TIMP1 [161], UCN2 [162], SELE (selectin E) [163], ICAM1 [164], FOSL1 [165], AREG (amphiregulin) [166], PIM2 [167], SLC7A5 [168], CH25H [169], COL5A2 [170], SNAI1 [171], MXRA5 [172], EGR1 [173], TNFRSF17 [174], MDFI (MyoD family inhibitor) [175], SRGN (serglycin) [176], CEACAM6 [177], CCL11…”

Section: Discussionmentioning

confidence: 99%

“…Many pathways are associated with the pathogenesis of CD. [124], TLR8 [125], HTRA3 [126], CEBPB (CCAAT enhancer binding protein beta) [127], CD55 [128], CXCR2 [129], CCL28 [130], CBR3 [131], CCL3 [132], FCGR2A [48], ACSL1 [133], CCL2 [134], SOD2 [135], CD14 [136], IGFBP2 [137], CD274 [138], DERL3 [139], SERPINE1 [140], IDO1 [141], PDK1 [142] [156], TYMP (thymidine phosphorylase) [144], S100P [157], PDPN (podoplanin) [158], ADAMTS1 [159], ATF3 [160], TIMP1 [161], UCN2 [162], SELE (selectin E) [163], ICAM1 [164], FOSL1 [165], AREG (amphiregulin) [166], PIM2 [167], SLC7A5 [168], CH25H [169], COL5A2 [170], SNAI1 [171], MXRA5 [172], EGR1 [173], TNFRSF17 [174], MDFI (MyoD family inhibitor) [175], SRGN (serglycin) [176], CEACAM6 [177], CCL11 [178], IFNG (interferon gamma) [179], TREM2 [180], INHBA (inhibin subunit beta A) [181], APOE (apolipoprotein E) [182], FGR (FGR proto-oncogene, Src family tyrosine kinase) GBP5 [465], HGF (hepatocyte growth factor) [466], CXCL9 [467], SLC11A1 [468], IL1RN [469], STAT1 [470], CYP27B1 [471], MMP1 [472], SOCS3 [473], TLR8 [474], CD55 [475], CCL28 [476], FCGR2A [477], CCL2 [478],...…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Pediatric Crohn's Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim of this investigation is to identify the key genes in CD and uncover their potential functions. We downloaded the next generation sequencing (NGS) dataset GSE73374 from the Gene Expression Omnibus (GEO) database. The NGS dataset GSE73374 was used to screen differentially expressed genes (DEGs) between samples from patients with CD and healthy controls. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Subsequently, a protein - protein interaction (PPI) network, modules, miRNA- hub gene regulatory network and TF - hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Receiver operating characteristic curve (ROC) analysis was applied to validate the hub genes. A total of 957 DEGs were identified, including 478 up regulated genes and 479 down regulated genes. GO and REACTOME results suggested that several Go terms and pathways are involved in response to stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system and biological oxidations. The top centrality hub genes MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 and TMEM25 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation identified key genes and signal pathways, which might help us improve our understanding of the molecular mechanisms of CD and identify some novel therapeutic targets for CD.

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“…Human HT29 and HCT116 cell lines were grown in McCoy’s 5A media (Gibco, CA, USA) containing 10% FBS and penicillin/streptomycin at 37°C in a 5% CO₂ incubator ( Yang et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Primers used for qPCR are compiled in Supplementary Table S1 . A Real-Time PCR system (BIOER Co. Ltd., Kokyo, Japan) was used for all qPCR analyses, and the relative expression of CLDN11, CLDN4, and TGFβ1 was assessed via the ΔCT method as in prior reports ( Yang et al, 2021 ). For appropriate experiments, the HT29 and HCT116 cells were treated for 48 h with the TGFβ1 inhibitor LY364947 (5.00 or 10.0uM).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer

Yang

Zhang

et al. 2022

Front. Genet.

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Background: Claudins (CLDNs) are a family of closely related transmembrane proteins that have been linked to oncogenic transformation and metastasis across a range of cancers, suggesting that they may be valuable diagnostic and/or prognostic biomarkers that can be used to evaluate patient outcomes. However, CLDN expression patterns associated with colorectal cancer (CRC) remain to be defined.Methods: The mRNA levels of 21 different CLDN family genes were assessed across 20 tumor types using the Oncomine database. Correlations between these genes and patient clinical outcomes, immune cell infiltration, clinicopathological staging, lymph node metastasis, and mutational status were analyzed using the GEPIA, UALCAN, Human Protein Atlas, Tumor Immune Estimation Resource, STRING, Genenetwork, cBioportal, and DAVID databases in an effort to clarify the potential functional roles of different CLDN protein in CRC. Molecular docking analyses were used to probe potential interactions between CLDN4 and TGFβ1. Levels of CLDN4 and CLDN11 mRNA expression in clinical CRC patient samples and in the HT29 and HCT116 cell lines were assessed via qPCR. CLDN4 expression levels in these 2 cell lines were additionally assessed following TGFβ1 inhibitor treatment.Results: These analyses revealed that COAD and READ tissues exhibited the upregulation of CLDN1, CLDN2, CLDN3, CLDN4, CLDN7, and CLDN12 as well as the downregulation of CLDN5 and CLDN11 relative to control tissues. Higher CLDN11 and CLDN14 expression as well as lower CLDN23 mRNA levels were associated with poorer overall survival (OS) outcomes. Moreover, CLDN2 and CLDN3 or CLDN11 mRNA levels were significantly associated with lymph node metastatic progression in COAD or READ lower in COAD and READ tissues. A positive correlation between the expression of CLDN11 and predicted macrophage, dendritic cell, and CD4+ T cell infiltration was identified in CRC, with CLDN12 expression further being positively correlated with CD4+ T cell infiltration whereas a negative correlation was observed between such infiltration and the expression of CLDN3 and CLDN15. A positive correlation between CLDN1, CLDN16, and neutrophil infiltration was additionally detected, whereas neutrophil levels were negatively correlated with the expression of CLDN3 and CLDN15. Molecular docking suggested that CLDN4 was able to directly bind via hydrogen bond with TGFβ1. Relative to paracancerous tissues, clinical CRC tumor tissue samples exhibited CLDN4 and CLDN11 upregulation and downregulation, respectively. LY364947 was able to suppress the expression of CLDN4 in both the HT29 and HCT116 cell lines.Conclusion: Together, these results suggest that the expression of different CLDN family genes is closely associated with CRC tumor clinicopathological staging and immune cell infiltration. Moreover, CLDN4 expression is closely associated with TGFβ1 in CRC, suggesting that it and other CLDN family members may represent viable targets for antitumor therapeutic intervention.

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CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1

Cited by 11 publications

References 35 publications

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer

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