Transcriptome analysis of basal and luminal tumor-initiating cells in ErbB2-driven breast cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

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TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer

Nature Communications ◽

10.1038/s41467-021-24703-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jiahui Xu ◽

Xiaoli Yang ◽

Qiaodan Deng ◽

Cong Yang ◽

Dong Wang ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Breast Tumor ◽

Breast Cancer Cells ◽

Triple Negative ◽

Vasculogenic Mimicry ◽

Regulatory Mechanisms ◽

Tumor Initiating Cells ◽

Self Renewal ◽

Tumor Endothelial Marker 8

AbstractEnhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.

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Prognostic biomarker identification and tumor classification in breast cancer patients by methylation and transcriptome analysis

FEBS Open Bio ◽

10.1002/2211-5463.13211 ◽

2021 ◽

Author(s):

Xiongdong Zhong ◽

Guoying Zhong

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Transcriptome Analysis ◽

Prognostic Biomarker ◽

Tumor Classification ◽

Breast Cancer Patients ◽

Biomarker Identification

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Transcriptome analysis of Notch2 High Breast Cancer (BrCa) cells revealed new molecular determinants of BrCa cellular dormancy in the bone/bone marrow microenvironment

Bone Reports ◽

10.1016/j.bonr.2021.100791 ◽

2021 ◽

Vol 14 ◽

pp. 100791

Author(s):

Michela Ciocca ◽

Antonio Maurizi ◽

Iona Norwood ◽

Nadia Rucci ◽

Anna Teti

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Transcriptome Analysis ◽

Bone Marrow Microenvironment ◽

Molecular Determinants

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The role of steroid hormones in breast cancer stem cells

Endocrine Related Cancer ◽

10.1530/erc-15-0350 ◽

2015 ◽

Vol 22 (6) ◽

pp. T177-T186 ◽

Cited By ~ 21

Author(s):

Bruno M Simões ◽

Denis G Alferez ◽

Sacha J Howell ◽

Robert B Clarke

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Steroid Hormones ◽

Normal Mammary Gland ◽

Breast Cancer Stem Cells ◽

Tumor Initiating Cells ◽

Unit Of Selection ◽

Selection For

Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity.

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