Resistance of primary breast cancer cells with enhanced pluripotency and stem cell activity to sex hormonal stimulation and suppression

Nasr, Mostafa; Farghaly, Mohamed; Elsaba, Tarek M.; El‐Mokhtar, Mohamed A.; Radwan, Radwa; Elsabahy, Mahmoud; Abdel-Kareem, Ahmed H.; Fakhry, Hussein; Mousa, Noha A.

doi:10.1016/j.biocel.2018.10.005

Cited by 9 publications

(10 citation statements)

References 86 publications

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“… 22 Breast cancer cells can establish a pluripotent program with enhanced stemness activity that is associated with resistance to sex hormone stimulation or deprivation. 23 Hematopoiesis presents a novel opportunity for limiting bone metastasis in breast cancer patients. This can be achieved through the hematopoietic myeloid/osteoclast progenitor cell lineage potential, and biomarkers that stratify responses among patients with high recurrence risks.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients

Tang

Zhou

2021

Cancer Control

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Background: Epigenetic changes are tightly linked to tumorigenesis development and malignant transformation’ However, DNA methylation occurs earlier and is constant during tumorigenesis. It plays an important role in controlling gene expression in cancer cells. Methods: In this study, we determining the prognostic value of molecular subtypes based on DNA methylation status in breast cancer samples obtained from The Cancer Genome Atlas database (TCGA). Results: Seven clusters and 204 corresponding promoter genes were identified based on consensus clustering using 166 CpG sites that significantly influenced survival outcomes. The overall survival (OS) analysis showed a significant prognostic difference among the 7 groups (p<0.05). Finally, a prognostic model was used to estimate the results of patients on the testing set based on the classification findings of a training dataset DNA methylation subgroups. Conclusions: The model was found to be important in the identification of novel biomarkers and could be of help to patients with different breast cancer subtypes when predicting prognosis, clinical diagnosis and management.

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Section: Discussionmentioning

confidence: 99%

DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients

Tang

Zhou

2021

Cancer Control

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“…This causes inevitable tumor invasion and metastasis, which is more common in TNBC than non-TNBC, ultimately resulting in poor prognosis. Studies have shown CSCs are associated with chemoresistance, particularly in TNBC due to the higher propensity of developing stemness compared to those found in non-TNBC [ 20 , 76 ].…”

Section: Chemoresistance In Triple Negative Breast Cancermentioning

confidence: 99%

The Role of Breast Cancer Stem Cells in Chemoresistance and Metastasis in Triple-Negative Breast Cancer

Wick

Germans

et al. 2021

Cancers

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Triple negative breast cancer (TNBC) remains an aggressive disease due to the lack of targeted therapies and relatively low rate of response to chemotherapy, which is currently the main treatment modality for TNBC. Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors and recognized as drivers of tumorigenesis. TNBC tumors are characterized as being enriched for BCSCs. Studies have demonstrated the role of BCSCs as the source of metastatic disease and chemoresistance in TNBC. Multiple targets against BCSCs are now under investigation, with the considerations of either selectively targeting BCSCs or co-targeting BCSCs and non-BCSCs (majority of tumor cells). This review article provides a comprehensive overview of recent advances in the role of BCSCs in TNBC and the identification of cancer stem cell biomarkers, paving the way for the development of new targeted therapies. The review also highlights the resultant discovery of cancer stem cell targets in TNBC and offers summaries of ongoing clinical trials treating chemoresistant breast cancer. We aim to better understand the mutational landscape of BCSCs and explore potential molecular signaling pathways targeting BCSCs to overcome chemoresistance and prevent metastasis in TNBC, ultimately to improve the overall survival of patients with this devastating disease.

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“…This concept is in accordance with the observations that endocrine treatment with either tamoxifen or fulvestrant reduced the proliferation of ER + ve cells with a concurrent increase of BCSCs [76] and that knockdown of FOXA1 attenuated MCF7 cell proliferation without impact on mammosphere formation [139]. Furthermore, Nasr et al have recently established a BC cell line from a ER+/PR+/HER2- tumor; the cell line consists of 92% ALDH1 + cells and 0.97–5.4% of CD44 + CD24 −/low cells, and OCT4, SOX2, and NANOG were overexpressed, suggesting the line being essentially cells with BCSC properties [140]. Intriguingly, treating these cells with either estrogen, progesterone, or their inhibitors for six months did not affect cell proliferation [140]; however, the ER status in the cell line prior to and after treatments has not been documented [140].…”

Section: Mechanisms Underlying Bcsc Enrichment Following the Develmentioning

confidence: 99%

“…Furthermore, Nasr et al have recently established a BC cell line from a ER+/PR+/HER2- tumor; the cell line consists of 92% ALDH1 + cells and 0.97–5.4% of CD44 + CD24 −/low cells, and OCT4, SOX2, and NANOG were overexpressed, suggesting the line being essentially cells with BCSC properties [140]. Intriguingly, treating these cells with either estrogen, progesterone, or their inhibitors for six months did not affect cell proliferation [140]; however, the ER status in the cell line prior to and after treatments has not been documented [140].…”

Section: Mechanisms Underlying Bcsc Enrichment Following the Develmentioning

confidence: 99%

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The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

Rodriguez

Ramkairsingh

Lin

et al. 2019

Cancers

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Breast cancer stem cells (BCSC) play critical roles in the acquisition of resistance to endocrine therapy in estrogen receptor (ER)-positive (ER + ve) breast cancer (BC). The resistance results from complex alterations involving ER, growth factor receptors, NOTCH, Wnt/β-catenin, hedgehog, YAP/TAZ, and the tumor microenvironment. These mechanisms are likely converged on regulating BCSCs, which then drive the development of endocrine therapy resistance. In this regard, hormone therapies enrich BCSCs in ER + ve BCs under both pre-clinical and clinical settings along with upregulation of the core components of “stemness” transcriptional factors including SOX2, NANOG, and OCT4. SOX2 initiates a set of reactions involving SOX9, Wnt, FXY3D, and Src tyrosine kinase; these reactions stimulate BCSCs and contribute to endocrine resistance. The central contributions of BCSCs to endocrine resistance regulated by complex mechanisms offer a unified strategy to counter the resistance. ER + ve BCs constitute approximately 75% of BCs to which hormone therapy is the major therapeutic approach. Likewise, resistance to endocrine therapy remains the major challenge in the management of patients with ER + ve BC. In this review we will discuss evidence supporting a central role of BCSCs in developing endocrine resistance and outline the strategy of targeting BCSCs to reduce hormone therapy resistance.

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Resistance of primary breast cancer cells with enhanced pluripotency and stem cell activity to sex hormonal stimulation and suppression

Cited by 9 publications

References 86 publications

DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients

DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients

The Role of Breast Cancer Stem Cells in Chemoresistance and Metastasis in Triple-Negative Breast Cancer

The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

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