DDR1 promotes migration and invasion of breast cancer by modulating the Src-FAK signaling

Qing, Han; Xiao, Fei; Ma, Lili; Zhou, Jinyuan; Wang, Lan; Cheng, Huang; Zhu, Jianmin; Yao, Fuli; Lyu, Jianxin; Du, Linyong

doi:10.4149/neo_2022_220316n289

Cited by 15 publications

(5 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, DDR1, RUNX1, and CBFβ have all garnered attention as potential clinical targets in breast cancer (Ariffin, 2022; Fowler et al, 2020; Han et al, 2022; Khawaled and Aqeilan, 2017; Malik et al, 2019). Current evidence indicates that RUNX1 and CBFβ are among the 30 most frequently mutated genes in breast cancer (Banerji et al, 2012; Koboldt et al, 2012; Pereira et al, 2016), with a prevalence of approximately 4-5% in breast cancer cases (Pereira et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation

Trepicchio,

Rauner,

Traugh

et al. 2024

Preprint

View full text Add to dashboard Cite

The human breast is complex and comprised of multi-lineage and multi-structural elements. Recent work has shown that epithelial stem and progenitor cells use the collagen receptor Discoidin Domain Receptor 1 (DDR1) for differentiation into both basal and luminal cell lineages, which together are necessary for both ductal and alveolar morphogenesis. We developed a next-generation single cell derived organoid model that generates miniaturized breast tissue, to study how single stem cells can give rise to multiple cell types and compound tissue structures. We show that DDR1 activation triggers stem cell differentiation via RUNX1 in turn driving multilineage differentiation as well as complex ductal-lobular development. Mechanistically, DDR1 affects the interaction and expression of RUNX1 and its cofactor CBFβ thereby regulating its activity. Together, these findings contribute to the current understanding of how the extracellular matrix component within the stem cell niche drives organogenesis and tissue regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation

Trepicchio,

Rauner,

Traugh

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Discoidin domain receptor 1 (DDR1) is a non-integrin collagen tyrosine kinase receptor, which is preferentially expressed in several malignancies and plays a key role in cancer progression and metastasis, especially in BC (Belfiore et al 2018 ). DDR1 is significantly increased in BC and inversely correlated with the prognosis of patients; DDR1 stimulates the migration and invasion of BC cells via activation of the Src-FAK signaling (Han et al 2022 ). In addition, DDR1 has been demonstrated to instigate immune evasion by promoting collagen fiber alignment (Sun et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

HNRNPC promotes collagen fiber alignment and immune evasion in breast cancer via activation of the VIRMA-mediated TFAP2A/DDR1 axis

Lian,

Yan,

et al. 2023

Mol Med

View full text Add to dashboard Cite

Background Cancers aggressively reorganize collagen in their microenvironment, leading to the evasion of tumor cells from immune surveillance. However, the biological significance and molecular mechanism of collagen alignment in breast cancer (BC) have not been well established. Methods In this study, BC-related RNA-Seq data were obtained from the TCGA database to analyze the correlation between DDR1 and immune cells. Mouse BC cells EO771 were selected for in vitro validation, and dual-luciferase experiments were conducted to examine the effect of TFAP2A on DDR1 promoter transcription activity. ChIP experiments were performed to assess TFAP2A enrichment on the DDR1 promoter, while Me-RIP experiments were conducted to detect TFAP2A mRNA m6A modification levels, and PAR-CLIP experiments were conducted to determine VIRMA’s binding to TFAP2A mRNA and RIP experiments to investigate HNRNPC’s recognition of m6A modification on TFAP2A mRNA. Additionally, an in vivo mouse BC transplant model and the micro-physiological system was constructed for validation, and Masson staining was used to assess collagen fiber arrangement. Immunohistochemistry was conducted to identify the number of CD8-positive cells in mouse BC tumors and Collagen IV content in ECM, while CD8 + T cell migration experiments were performed to measure CD8 + T cell migration. Results Bioinformatics analysis showed that DDR1 was highly expressed in BC and negatively correlated with the proportion of anti-tumor immune cell infiltration. In vitro cell experiments indicated that VIRMA, HNRNPC, TFAP2A, and DDR1 were highly expressed in BC cells. In addition, HNRNPC promoted TFAP2A expression and, therefore, DDR1 transcription by recognizing the m6A modification of TFAP2A mRNA by VIRMA. In vivo animal experiments further confirmed that VIRMA and HNRNPC enhanced the TFAP2A/DDR1 axis, promoting collagen fiber alignment, reducing anti-tumor immune cell infiltration, and promoting immune escape in BC. Conclusion This study demonstrated that HNRNPC promoted DDR1 transcription by recognizing VIRMA-unveiled m6A modification of TFAP2A mRNA, which enhanced collagen fiber alignment and ultimately resulted in the reduction of anti-tumor immune cell infiltration and promotion of immune escape in BC.

show abstract

“…Integrins and DDRs bind to multiple ECM components, including type I collagen 21 . Both are overexpressed in breast cancer, where they promote cell migration, ECM degradation and metastasis formation 4,[22][23][24] . During cell migration, adhesion sites can be torn from the plasma membrane when cells migrate, leaving a trail of membrane debris on the ECM along the migration path.…”

Section: Introductionmentioning

confidence: 99%

Cancer cells transfer invasive properties through collagen-tracks

Saltel

Normand

Rouyer

et al. 2023

Preprint

View full text Add to dashboard Cite

Invasion and migration through the extracellular matrix are prerequisites for metastasis, the leading cause of cancer-related deaths. During tumor development, the extracellular matrix is remodeled, including by overexpressing type I collagen that facilitate cancer dissemination. Most studies have focused on events at the leading edge as cells invade. We describe a new event at the trailing edge, as cells detach from the matrix. We show that small vesicles containing the collagen receptor DDR1 are left behind on collagen fibrils in the migration path. We named these structures attached to the collagen fibers "collagen-tracks". The vesicles are similar in size to exosomes but lack the exosome markers, and they also are different to migrasomes. We show that collagen-track formation is stimulated by DDR1 and by factors that promote adhesion, including collagen cross-linking. We report the protein, mRNA and miRNA content of collagen-tracks. They contain adhesion proteins, suggesting that they form when membrane fragments containing adhesions are torn from the cell as it migrates along collagen fibrils. We show that collagen-tracks are deposited by breast cancer cells in 3D matrices in vitro and in vivo. Collagen-tracks are stable and can be taken up by surrounding cells, promoting epithelial to mesenchymal transition, matrix degradation and invasion, finally leading to increased lung metastasis of breast cancer cells. In summary, we have identified and characterized a new vesicle entity directly attached to collagen fibrils that plays a role in cell-cell communication and can transfer invasive properties to surrounding cells. We conclude that cancer-related collagen-tracks are a new player acting locally to drive tumor invasion and metastasis

show abstract

DDR1 promotes migration and invasion of breast cancer by modulating the Src-FAK signaling

Cited by 15 publications

References 37 publications

DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation

DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation

HNRNPC promotes collagen fiber alignment and immune evasion in breast cancer via activation of the VIRMA-mediated TFAP2A/DDR1 axis

Cancer cells transfer invasive properties through collagen-tracks

Contact Info

Product

Resources

About