Molecular and cellular mechanisms underlying brain metastasis of breast cancer

Hosonaga, Mari; Saya, Hideyuki; Arima, Yoshimi

doi:10.1007/s10555-020-09881-y

Cited by 101 publications

(89 citation statements)

References 78 publications

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“…Currently, the primary prevention of BCa has not been achieved; therefore, strengthening secondary prevention, early detection, early diagnosis and early treatment methods may serve a vital role in reducing the mortality rates of patients with BCa, thereby improving the survival rates (24). Despite recent significant advances in understanding the mechanisms of BCa development and the improvement of treatment strategies, BCa remains the second leading cause of cancer-related mortality in women, and death is almost always due to metastasis (25). The prognosis of patients with metastatic BCa is poor, with an average 5-year survival rate of only 27% (26).…”

Section: Discussionmentioning

confidence: 99%

MST1 inhibits the progression of breast cancer by regulating the Hippo signaling pathway and may serve as a prognostic biomarker

et al. 2021

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Breast cancer (BCa) is the most common malignancy threatening the health of women worldwide, and the incidence rate has significantly increased in the last 10 years. Mammalian STE20-like protein kinase 1 (MST1) is involved in the development of various types of malignant tumor. The present study aimed to investigate the role of MST1 in BCa and its potential involvement in the poor prognosis of patients with BCa. Reverse transcription-quantitative PCR and immunohistochemistry were used to analyze the expression levels of MST1 in BCa, and the clinicopathological characteristics and prognosis of patients with BCa were further analyzed by statistical analysis. MST1 was overexpressed in BCa cell lines (MCF-7, MDA-MB-231 and SKBR3). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine and flow cytometry assays were used to analyze cell proliferation and apoptosis, respectively, and a wound healing assay was used to analyze cell migration. The results of the present study revealed that the downregulated expression levels of MST1 in BCa were closely associated with the poor prognosis of patients, and MST1 may be an independent risk factor for BCa. The overexpression of MST1 significantly inhibited the proliferation and migration, and promoted the apoptosis of BCa cells. In addition, the overexpression of MST1 significantly activated the Hippo signaling pathway. Treatment with XMU-MP-1 downregulated the expression levels of MST1 and partially reversed the inhibitory effects of MST1 on proliferation, migration and apoptosis-related proteins, and inhibited the Hippo signaling pathway. In conclusion, the results of the present study suggested that MST1 expression levels may be downregulated in BCa and closely associated with tumor size and clinical stage, as well as the poor prognosis of affected patients. Furthermore, MST1 may inhibit the progression of BCa by targeting the Hippo signaling pathway.

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Section: Discussionmentioning

confidence: 99%

MST1 inhibits the progression of breast cancer by regulating the Hippo signaling pathway and may serve as a prognostic biomarker

et al. 2021

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“…We also observed that treating the cells with AOH decreased the expression of protein kinase B (Akt) and Erk1/2 (p44/42) and their phosphorylated forms ( Figure 9 ). Phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPK) signaling pathways are the key intracellular pathways in breast cancer responsible for the proliferation and metastases [ 23 ]. We observed that AOH decreased both expression of Akt and p44/42, as well as its phosphorylated forms ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Mycotoxin Alternariol (AOH) Affects Viability and Motility of Mammary Breast Epithelial Cells

Kowalska

Habrowska-Górczyńska

Kozieł

et al. 2021

IJMS

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Mycotoxins are present in everyday diet as common food and feed pollutants. A part of them is still concerned as so-called emerging mycotoxins. Due to the lack of toxicity data, the safety limits and detail molecular mechanism have been not established yet for all of them. Alternariol (AOH), as one of these mycotoxins, produced by Alternaria species, is so far reported as an estrogenic, genotoxic, and immunomodulatory agent; however, its direct effect on human health is not known. Especially, in the case of hormone-dependent tissues which are sensitive to both endogenic, as well as external estrogenic agents, it might be crucial to assess the effect of AOH. Thus, this study evaluated how exposure to AOH affects viability and motility of the human normal mammary gland epithelial in vitro model. We observed that AOH significantly affects viability of cells in a time- and dose-dependent manner. Moreover, the induction of oxidative stress, DNA damage, and cell cycle arrest in the G2/M cell cycle phase was observed. The motility of 184A1 cells was also significantly affected. On the molecular level, AOH induced antioxidative stress response via activation of Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway agents, as well as decrease in the phosphorylation of protein kinase B (Akt) and p44/42 (ERK 1-2) molecules, indicating that AOH might affect crucial signaling pathways in both physiological and pathophysiological processes in breast tissue.

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“…This is mediated by the binding of STAT3+ reactive astrocytes associated with brain metastases that present an increased expression of macrophage migration inhibitory factor (MIF), which binds to CD74+ microglia that contributes to the establishment of an immunosuppressive microenvironment. Such activated microglia present upregulation of midkine, a downstream target of NF-kB signaling pathway that promotes the development of brain metastases [ 174 ]. The acquisition of neurons-like properties by BCCs can also support brain metastases development.…”

Section: Mirnas In Breast Cancer Brain Metastasesmentioning

confidence: 99%

miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Sereno

Videira

Wilhelm

et al. 2020

Cells

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MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

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Molecular and cellular mechanisms underlying brain metastasis of breast cancer

Cited by 101 publications

References 78 publications

MST1 inhibits the progression of breast cancer by regulating the Hippo signaling pathway and may serve as a prognostic biomarker

MST1 inhibits the progression of breast cancer by regulating the Hippo signaling pathway and may serve as a prognostic biomarker

Mycotoxin Alternariol (AOH) Affects Viability and Motility of Mammary Breast Epithelial Cells

miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

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