DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma

Cardin, Guillaume B.; Bernard, Monique; Rodier, Françis; Christopoulos, Apostolos

doi:10.1038/s41598-021-92090-6

Cited by 6 publications

(4 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been established that the integrin pathway will be triggered upon binding with ECM, accompanied by activation of downstream actin reorganization and MAPK signaling cascade (40). In HNSCC, the integrin pathway is involved in disease progression, tumor stem cells, and radioresistance (41,42). We also noted that GO annotations related to DCBLD1 gene included focal adhesion, cell-substrate junction, ECM organization, cell adhesion molecule binding, and other biological processes involved in ECM and cell adhesion.…”

Section: Discussionmentioning

confidence: 76%

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma

Yan²,

Ma³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundDCBLD1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the prognostic value and immune infiltration in head and neck squamous cell carcinoma remain unclear and need further research.Materials and MethodsDCBLD1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. The mRNA level in cell lines (SCC25 and CAL27) and gingival fibroblasts were detected using quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of DCBLD1 and clinical data in HNSCC. A nomogram was also established to predict the impact of DCBLD1 on prognosis based on Cox multivariate results. The methylation level of DCBLD1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of DCBLD1 were investigated using gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA).ResultsThe mRNA and protein expression levels of DCBLD1 were highly expressed in HNSCC tissue and cell lines. The Cox analyses demonstrate that highly expressed DCBLD1 is an independent prognosis marker (p < 0.05). ROC curve analysis showed the performance of DCBLD1 (area under the ROC curve: 0.948, sensitivity: 93.2%, specificity: 84.7%). The methylation was increased in HNSCC patients compared with normal subjects (p < 0.05) and was associated with poor prognosis at sites cg27642470 and cg21104965. Additionally, DCBLD1 expression is poorly associated with immune cell infiltration and immunological checkpoints PD-L1 and TIM-3.ConclusionIn head and neck squamous cell carcinoma, DCBLD1 is overexpressed, associated with poor patient prognosis. The detailed underlying mechanism merits further research.

show abstract

Section: Discussionmentioning

confidence: 76%

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma

Yan²,

Ma³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…A previous study showed that single nucleotide polymorphisms of promoter region of DCBLD1 was associated with head and neck cancer and lung cancer in never-smoking women (46)(47)(48)(49). Analysis of TCGA analysis demonstrated that expression of DCBLD1 was associated with worse prognosis in the patients with nonsmall cell lung cancer and invasive breast cancer (50). Notably, high expression of DCBLD1 was associated with the integrin signaling pathway (50).…”

Section: Figure 6 Effects Of Rrm2 Knockdown In Pdac Cells Validation ...mentioning

confidence: 98%

“…Analysis of TCGA analysis demonstrated that expression of DCBLD1 was associated with worse prognosis in the patients with nonsmall cell lung cancer and invasive breast cancer (50). Notably, high expression of DCBLD1 was associated with the integrin signaling pathway (50). Expression of these genes is promising as a prognostic marker for patients with PDAC.…”

Section: Figure 6 Effects Of Rrm2 Knockdown In Pdac Cells Validation ...mentioning

confidence: 99%

Impact of Oncogenic Targets Controlled by Tumor-Suppressive miR-30a-5p in Pancreatic Ductal Adenocarcinoma

et al. 2021

View full text Add to dashboard Cite

Background/Aim: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease. Materials and Methods: In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples. Results: A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells. Conclusion: The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer with the highest mortality rate among various human cancers (1, 2). The 5-year survival rate for patients with PDAC is around 8%, and approximately 459,000 people were diagnosed with PDAC and 432,000 died in 2018 (3). A notable feature of PDAC is that patients have few symptoms in the early stages of disease. By the

show abstract

“…DCBLD1 is a gene encoding unknown membrane proteins, which are over-expressed in lung adenocarcinoma. Additionally, it is reported to be a prognostic factor for overall survival of non-small cell lung carcinoma (NSCLC) and breast cancer 11,12 . The expression of DCBLD1 can be inhibited by creating YY1 binding sites, which reduce the risk of lung adenocarcinoma 12 .…”

Section: Introductionmentioning

confidence: 99%

DCBLD1 modulates angiogenesis by regulating of the VEGFR-2 endocytosis in endothelial cells

Guo

et al. 2023

Preprint

View full text Add to dashboard Cite

ObjectiveUnwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (Discoidin, CUB, and LCCL domain-containing protein 1) is a co-receptor of VEGFR-2 and modulates angiogenesis in endothelial cells(ECs).Approach and ResultsA carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or EC-specific conditional DCBLD1 knockout micein vivo. Immunoblotting, immunofluorescence staining, plasma-membrane subfraction isolation, Co-immunoprecipitation and mass-spectrum assay were performed to clarify the molecular mechanisms.Loss of DCBLD1 impaired VEGF response and inhibited VEGF-induced EC proliferation and migration. DCBLD1 deletion interfered with adult and developmental angiogenesis. Mechanistically, DCBLD1 bound to VEGFR-2 and regulated the formation of VEGFR-2 complex with negative regulators: protein tyrosine phosphatases, E3 ubiquitin ligases(Nedd4 and c-Cbl), and also DCBLD1 knockdown promoted lysosome-mediated VEGFR-2 degradation in ECs.ConclusionsThese findings demonstrated the essential role of endothelial DCBLD1 in regulating VEGF signaling and provided evidence that DCBLD1 promotes VEGF-induced angiogenesis by limiting the dephosphorylation, ubiquitination, and lysosome degradation after VEGFR-2 endocytosis. We proposed that endothelial DCBLD1 is a potential therapeutic target for ischemic cardiovascular diseases by the modulation of angiogenesis through regulating of the VEGFR-2 endocytosis.

show abstract

DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma

Cited by 6 publications

References 54 publications

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma

Impact of Oncogenic Targets Controlled by Tumor-Suppressive miR-30a-5p in Pancreatic Ductal Adenocarcinoma

DCBLD1 modulates angiogenesis by regulating of the VEGFR-2 endocytosis in endothelial cells

Contact Info

Product

Resources

About