Overexpression of DDR1 Promotes Migration, Invasion, Though EMT-Related Molecule Expression and COL4A1/DDR1/MMP-2 Signaling Axis

Xie, Xin; He, Hongchao; Zhang, Ning; Wang, Xiaojing; Wu, Rui; Xu, Danfeng; Zhu, Yu

doi:10.1177/1533033820973277

Cited by 15 publications

(12 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, we demonstrated that DDR1 promotes thyroid cancer cell dedifferentiation and the acquisition of a stemlike phenotype by enhancing the IGF-2/IR-A autocrine signaling loop [9,10] and plays a critical role in promoting bladder cancer cell motility by linking the IGF1R and IR-A to the regulation of F-actin cytoskeleton dynamics [15]. Collectively, these data uncover novel, non-canonical DDR1 functions, which strongly support the pro-tumorigenic and pro-metastatic role of DDR1 [16][17][18].…”

Section: Introductionsupporting

confidence: 60%

DDR1 Affects Metabolic Reprogramming in Breast Cancer Cells by Cross-Talking to the Insulin/IGF System

et al. 2021

View full text Add to dashboard Cite

The insulin receptor isoform A (IR-A), a dual receptor for insulin and IGF2, plays a role in breast cancer (BC) progression and metabolic reprogramming. Notably, discoidin domain receptor 1 (DDR1), a collagen receptor often dysregulated in cancer, is involved in a functional crosstalk and feed forward loop with both the IR-A and the insulin like growth factor receptor 1 (IGF1R). Here, we aimed at investigating whether DDR1 might affect BC cell metabolism by modulating the IGF1R and/or the IR. To this aim, we generated MCF7 BC cells engineered to stably overexpress either IGF2 (MCF7/IGF2) or the IR-A (MCF7/IR-A). In both cell models, we observed that DDR1 silencing induced a significant decrease of total ATP production, particularly affecting the rate of mitochondrial ATP production. We also observed the downregulation of key molecules implicated in both glycolysis and oxidative phosphorylation. These metabolic changes were not modulated by DDR1 binding to collagen and occurred in part in the absence of IR/IGF1R phosphorylation. DDR1 silencing was ineffective in MCF7 knocked out for DDR1. Taken together, these results indicate that DDR1, acting in part independently of IR / IGF1R stimulation, might work as a novel regulator of BC metabolism and should be considered as putative target for therapy in BC.

show abstract

Section: Introductionsupporting

confidence: 60%

DDR1 Affects Metabolic Reprogramming in Breast Cancer Cells by Cross-Talking to the Insulin/IGF System

et al. 2021

View full text Add to dashboard Cite

show abstract

“…EMT plays a vital role in tumour invasion and progression, including tumour initiation, malignant progression, tumour cell migration, metastasis, and treatment resistance of tumours 42 . During EMT, the polarized epithelial cells lose their tight intercellular junctions to gradually differentiate into cells with mesenchymal properties, allowing rapid cell migration and large collagen formation 43,44 . DDR1 participates in many cancers, including prostate cancer, 45 liver cancer, 46 gastric cancer, 47 kidney cancer, 48 osteosarcoma, 49 and colorectal cancer 50 .…”

Section: Resultsmentioning

confidence: 99%

“…DDR1 mediates the EMT process, tumour invasion, and metastasis. DDR1 can participate in the EMT through the following mechanism 44,51,53,54 DDR1 regulates EMT through cadherin switching The switching of epithelial phenotype E‐cadherin into mesenchymal phenotypes, such as N‐cadherin and vimentin, is a characteristic of EMT 55,56 .…”

Section: Resultsmentioning

confidence: 99%

Discoidin domain receptor 1 may be involved in biological barrier homeostasis

Chen

Zhang

2022

Clinical Pharmacy Therapeu

View full text Add to dashboard Cite

What is known and objective: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase involved in the pathological processes of several diseases, such as keloid formation, renal fibrosis, atherosclerosis, tumours, and inflammatory processes. The biological barrier is the first line of defence against pathogens, and its disruption is closely related to diseases. In this review, we attempt to elucidate the relationship between DDR1 and the biological barrier, explore the potential biological value of DDR1, and review the current research status and clinical potential of DDR1-selective inhibitors. Methods:We conducted an extensive literature search on PubMed to collect studies on the relevance of DDR1 to biological barriers and DDR1-selective inhibitors. With these studies, we explored the relationship between DDR1 and biological barriers and briefly reviewed representative DDR1-selective inhibitors that have been reported in recent years.Results and discussion: First, the review of the potential mechanisms by which DDR1 regulates biological barriers, including the epithelial, vascular, glomerular filtration, blood-labyrinth, and blood-brain barriers. In the body, DDR1 dysfunction and aberrant expression may be involved in the homeostasis of the biological barrier. Secondly, the review of DDR1 inhibitors reported in recent years shows that DDR1-targeted inhibi-

show abstract

“…Ambrogio et al reported that DDR1 could be a therapeutic target for KRAS-driven non-small-cell lung cancer [ 44 ]. Another primary study revealed that in bladder cancer upregulation of DDR1 could promote invasion and migration via the EMT pathway [ 45 ]. Considering the above research results which can be used as the verification of our bioinformatics results, it may indicate that COL3A1 may act as a molecular biomarker mediating in several pathways of human cancer development.…”

Section: Discussionmentioning

confidence: 99%

Data mining-based study of collagen type III alpha 1 (COL3A1) prognostic value and immune exploration in pan-cancer

Zhang

Ding

et al. 2021

Bioengineered

View full text Add to dashboard Cite

The extracellular matrix (ECM) shows an essential effect during the occurrence and procession of human cancers. Type III collagen is a crucial component of ECM. Collagen Type III Alpha 1 (COL3A1) is aberrantly expressed in a variety of cancers. Nevertheless, the role of COL3A1 in pancancer stays unidentified. In this study, we explored public databases, including Cancer Genome Atlas (TCGA), GTEx, GEPIA, cBioPortal, Oncommine, TIMER and GENEMANIA databases to identify the differential expression of COL3A1 in human cancer tissues and normal samples, followed by its prognostic value for patient survival. In addition, we explore the association between COL3A1 expression and immune infiltration. Further, we used the GeneMANIA database and Gene Set Enrichment Analysis (GSEA) to investigate Protein-Protein Interaction (PPI) and gene functional enrichment. Results show that COL3A1 expressed higher in tumor samples than in normal samples. Upregulation of COL3A1 is associated with a worse prognosis and a more advanced cancer stage. COL3A1 expression shows significant positive correlations with tumor-infiltrating immune cells (TIICs), including neutrophils, macrophages, CD8 + T cells, CD4 + T cells, dendritic cells, and B cells. Markers of TIICs demonstrated distinct patterns of COL3A1-related immune infiltration. COL3A1 expression was associated with ECM receptor interaction, regulation of actin cytoskeleton and focal adhesion pathways via GSEA analysis. In conclusion, COL3A1 may be a molecular biomarker for prognosis and immune infiltration in pan-cancer. It might act as a potential target for a new insight of human cancers management.

show abstract

Overexpression of DDR1 Promotes Migration, Invasion, Though EMT-Related Molecule Expression and COL4A1/DDR1/MMP-2 Signaling Axis

Cited by 15 publications

References 51 publications

DDR1 Affects Metabolic Reprogramming in Breast Cancer Cells by Cross-Talking to the Insulin/IGF System

DDR1 Affects Metabolic Reprogramming in Breast Cancer Cells by Cross-Talking to the Insulin/IGF System

Discoidin domain receptor 1 may be involved in biological barrier homeostasis

Data mining-based study of collagen type III alpha 1 (COL3A1) prognostic value and immune exploration in pan-cancer

Contact Info

Product

Resources

About