DDR1 promotes breast tumor growth by suppressing antitumor immunity

Zhong, Xing; Zhang, Weiwei; Sun, Tianhao

doi:10.3892/or.2019.7338

Cited by 29 publications

(27 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…How DDRs induce cancer signaling is another critical question, although we established an important connection between DDR1 signaling and the β-catenin pathway (42). Last, but not least, recent reports uncovered unsuspected DDR roles in CRC immune evasion (61,62). How these receptors contribute to this cancer hallmark is a basic and clinical question because DDR signaling inhibition could define a therapeutic strategy to reduce metastatic development and sensitize CRC to immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 87%

“…Whether DDR2 has a similar role in microsatellite-stable CRC cells remains to be tested. Similarly, it was suggested that DDR1 promotes breast tumor growth by suppressing the anti-tumor immunity (62). How exactly and in which circumstances DDR1 and DDR2 may regulate human tumor evasion, particularly in CRC, deserve further investigation.…”

Section: Ddr2 In Crc Metastasesmentioning

confidence: 99%

“…For instance, anti-DDR1 antibodies can interfere with DDR1 binding to collagens, by sterically blocking the extracellular association of DDR1 subunits ( Table 1) (73). Similarly, a neutralizing antibody against DDR1 inhibits breast tumor growth in a mouse model by suppressing the anti-tumor immunity (62). Due to DDR1 aberrant expression in CRC, an anti-DDR1 antibody-drug conjugate was recently developed for CRC treatment.…”

Section: Targeting Ddr Tumor Activity In Metastatic Crcmentioning

confidence: 99%

See 2 more Smart Citations

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

2020

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide. While surgery can cure patients with early stage CRC, the 5-year survival rate is only 10% for patients with metastatic disease. Therefore, new anti-metastatic therapies are needed for this cancer. Metastatic spread defines the dissemination of cancer cells with tumor-initiating capacities from the primary tumor and their colonization of distinct organs, mainly the liver, for secondary tumor formation. Although the underlying mechanisms are not fully understood, components of the tumor microenvironment have gained strong interest. Among the known metastatic-promoting factors, collagens are extracellular matrix components that are deposited within the tumor, the tumor microenvironment, and at metastatic site(s), and are recognized to play essential roles during metastasis development. Here, we review recent findings on the metastatic role of the collagen receptors Discoidin Domain Receptors 1 and 2 (DDR1 and DDR2) in CRC and discuss the therapeutic value of targeting these receptor tyrosine kinases in this cancer.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Ddr2 In Crc Metastasesmentioning

confidence: 99%

Section: Targeting Ddr Tumor Activity In Metastatic Crcmentioning

confidence: 99%

See 1 more Smart Citation

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

2020

View full text Add to dashboard Cite

show abstract

“…First, COL8A1 products belong to extracellular matrix protein and serve as one of the nineteen human collagens, which are important components of the breast cancer stroma. It is possible that COL8A1 participates in the communication of breast cancer cells and microenvironments [61]. Second, COL8A1 plays important role in modulating migration, proliferation, and adhesion of tumor cells [62].…”

Section: Discussionmentioning

confidence: 99%

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Wei

Zeng

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and coexpressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

show abstract

“…36 For example, Zhong et al disclosed that DDR1 augmentation induced tumorigenesis via hindering antitumor immunity in breast cancer. 37 Chou et al found that suppression of DDR1 restrained cell growth and accelerated apoptosis in oral cancer. 38 Moreover, the previous study indicated that DDR1 silencing impeded tumor progression in CRC by interacting with miR-199a-5p.…”

Section: Discussionmentioning

confidence: 99%

<p>Circ-PRKDC Facilitates the Progression of Colorectal Cancer Through miR-198/DDR1 Regulatory Axis</p>

Wang¹,

Li²,

Zhu³

et al. 2020

CMAR

View full text Add to dashboard Cite

Background Circular RNAs (circRNAs) play a crucial role in a variety of cancers, including colorectal cancer (CRC). This study aimed to explore the role of hsa_circ_0136666 ( circ-PRKDC ) in CRC and its potential mechanism. Methods The levels of circ-PRKDC , miR-198 and discoidin domain receptor 1 ( DDR1 ) were measured using quantitative real-time polymerase chain reaction or Western blot. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell apoptosis and cycle were evaluated via flow cytometry. Cell migration and invasion were examined using transwell assay. CyclinD1 protein level was determined via Western blot. The interaction among circ-PRKDC , miR-198 and DDR1 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was performed to analyze tumor growth in vivo. Results Circ-PRKDC and DDR1 levels were increased, and miR-198 level was decreased in CRC tissues and cells. Circ-PRKDC depletion inhibited proliferation, migration and invasion, and expedited apoptosis and cell cycle arrest in SW480 and HCT116 cells. Silence of circ-PRKDC impeded CRC progression by sponging miR-198 . Overexpression of miR-198 hindered CRC development via targeting DDR1 . Moreover, circ-PRKDC silencing suppressed tumor growth in vivo. Conclusion Knockdown of circ-PRKDC inhibited CRC progression via modulating miR-198 / DDR1 pathway.

show abstract

DDR1 promotes breast tumor growth by suppressing antitumor immunity

Cited by 29 publications

References 60 publications

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

<p>Circ-PRKDC Facilitates the Progression of Colorectal Cancer Through miR-198/DDR1 Regulatory Axis</p>

Contact Info

Product

Resources

About