RUNX1 as a Novel Molecular Target for Breast Cancer

Ariffin, Nur Syamimi

doi:10.1016/j.clbc.2022.04.006

Cited by 9 publications

(7 citation statements)

References 59 publications

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“…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

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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.

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Section: Discussionmentioning

confidence: 99%

DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation

Trepicchio,

Rauner,

Traugh

et al. 2024

Preprint

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“…studies have revealed that RUNX1 mRNA is associated with metastasis of breast and prostate cancers, with expression inversely associated with tumour aggressiveness. 15,[23][24][25][26] Moreover, RUNX1 has been reported to be involved in several hormone-related solid cancers. 26 Beyond breast cancer, overexpression of RUNX1 was suggested to play a promotive role in endometrioid carcinoma myometrial infiltration.…”

Section: Discussionmentioning

confidence: 99%

“…It is also becoming evident that varying levels of RUNX1 expression can be identified as markers of tumour progression not only in haematopoietic system diseases but also in solid tumour diseases 16,22 . Earlier studies have revealed that RUNX1 mRNA is associated with metastasis of breast and prostate cancers, with expression inversely associated with tumour aggressiveness 15,23–26 . Moreover, RUNX1 has been reported to be involved in several hormone‐related solid cancers 26 .…”

Section: Discussionmentioning

confidence: 99%

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

Guo

Liu

Zhao

et al. 2023

Int J Experimental Path

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Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density‐gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual‐luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4‐induced conditions. Moreover, α‐SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF‐β/Smads in a dual‐luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF‐β/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.

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“…1 The development of novel targeted cancer therapy for breast cancer has become a critical target for medicinal chemists, especially to combat highly resistant cancer cells and the multiple side effects of chemotherapy. [2][3][4] Vascular endothelial growth factor (VEGF) exhibits a significant function in breast cancer development and metastasis, as evidenced by its elevated transcript levels in breast carcinoma. Its vital role in angiogenesis and vasculogenesis is initiated by the binding of VEGF and the VEGF receptor (VEGFR).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%