NOTCH expression variability and relapse of breast cancer in high-risk groups

Gómez-Archila, José Damián; Espinosa-García, Ana María; Palacios‐Reyes, Carmen; Trujillo-Cabrera, Yanelly; Mejía, Ana Lilia Sandoval; González, Ana Victoria De Alba; Rangel-López, Edgar; Alonso-Themann, Patricia García; Solís, Nereo Damaso Sandoval; Hernández-Zavala, Araceli; López, Pedro Grajeda; Contreras-Ramos, Alejandra; Palma‐Lara, Icela

doi:10.1016/j.amjms.2021.12.015

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…Considering the various causal factors of BC, there are several signaling pathways involved, such as the (human epidermal growth factor receptor (HER), NOTCH and β-catenin pathways, which are linked to the evolution of the disease, as demonstrated in in vitro studies ( 26 - 29 ) and in patient samples ( 30 - 32 ). In turn, these pathways are related to EBV components, promoting progression and cell survival and in some cases, resistance to anthracycline-based treatments.…”

Section: Epstein-barr Virus and Breast Cancermentioning

confidence: 99%

Epstein‑Barr virus as a promoter of tumorigenesis in the tumor microenvironment of breast cancer (Review)

et al. 2023

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Epstein-Barr virus (EBV) is an oncovirus associated with various neoplasms, including breast cancer (BC). EBV-associated oncogenesis requires the action of several viral molecules, such as EBV nuclear antigen 3C, latent membrane protein 1, microRNAs and long non-coding RNAs, which are able of manipulating the cellular machinery, inducing an evasion of the immune system, blocking apoptosis processes, promoting cell survival and metastasis. The risk of developing cancer is associated with epigenetic alterations and alterations in various signaling pathways. The activation of all these molecules can modify the expression of EBV proteins with oncogenic activity, influencing the oncogenic process. It is clear that BC, being multifactorial, presents a greater complexity; in numerous cases, the infection associated with EBV may be crucial for this neoplasia, if particular conditions for both the virus and host are present. In the present review, all these variables are analyzed in an aim to improve the understanding of the participation of EBV in BC.

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Section: Epstein-barr Virus and Breast Cancermentioning

confidence: 99%

Epstein‑Barr virus as a promoter of tumorigenesis in the tumor microenvironment of breast cancer (Review)

et al. 2023

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Prognostic and predictive impact of NOTCH1 in early breast cancer

Engel,

Wieder,

Bauer

et al. 2024

Breast Cancer Res Treat

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Purpose Systemic therapy plays a major part in the cure of patients with early breast cancer (eBC). However, personalized treatment concepts are required to avoid potentially harmful overtreatment. Biomarkers are pivotal for individualized therapy. The Notch signalling pathway is widely considered as a suitable prognostic or predictive marker in eBC. This study aimed primarily at assessing the relationship between NOTCH1 mRNA expression levels and histopathological features of breast cancer tumors, as well as clinical characteristics of the correspondent eBC patients. As a secondary aim, we investigated the prognostic and predictive value of NOTCH1 by assessing possible associations between NOTCH1 mRNA expression and recurrence-free interval (RFI) and overall survival after five years of observation. Patients and methods The relative NOTCH1 mRNA expression was determined in 414 tumour samples, using quantitative PCR in a prospective, multicenter cohort (Prognostic Assessment in Routine Application (PiA), 2009–2011, NCT01592825) of 1,270 female eBC patients. Results High NOTCH1 mRNA expression was detected in one-third of the tumours and was associated with negative hormone receptor status and high uPA/PAI-1 status. In addition, high NOTCH1 mRNA expression was found to be associated with more RFI related events (adjusted hazard ratio 2.1, 95% CI 1.077–4.118). Patients who received adjuvant chemotherapy and had high NOTCH1 mRNA expression in the tumour (n = 86) were three times more likely to have an RFI event (adjusted hazard ratio 3.1, 95% CI 1.321–7.245, p = 0.009). Conclusion In this cohort, NOTCH1 mRNA expression had a prognostic and predictive impact. Tumours with high NOTCH1 mRNA expression may be less sensitive to cytotoxic treatment and downregulation of the Notch signalling pathway (e.g. by γ-secretase inhibitors) may be valuable for eBC therapy as an individualised treatment option.

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TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway

Wang,

Wu,

et al. 2024

J Transl Med

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Background Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC. Methods Bioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC. Results GRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/β-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/β-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing. Conclusions Our work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-024-05536-6.

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NOTCH expression variability and relapse of breast cancer in high-risk groups

Cited by 3 publications

References 22 publications

Epstein‑Barr virus as a promoter of tumorigenesis in the tumor microenvironment of breast cancer (Review)

Epstein‑Barr virus as a promoter of tumorigenesis in the tumor microenvironment of breast cancer (Review)

Prognostic and predictive impact of NOTCH1 in early breast cancer

TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway

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