Signaling pathways governing breast cancer stem cells behavior

Song, Kai; Farzaneh, Maryam

doi:10.1186/s13287-021-02321-w

Cited by 78 publications

(62 citation statements)

References 170 publications

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“…Stemness-associated signaling cascades, such as the Wnt, Hedgehog and Notch pathways, regulate the maintenance of bCSCs (reviewed in [49]). Some of them are also involved in the induction of EMT that has been associated with the generation of bCSCs (reviewed in [50]).…”

Section: Trpm4 Regulates the Stemness Properties Of Bcscs In Vitromentioning

confidence: 99%

Transcriptional Profiling of Tumorspheres Reveals TRPM4 as a Novel Stemness Regulator in Breast Cancer

et al. 2021

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Cancer stem cells (CSCs) have been implicated in the development of chemoresistance, tumor recurrence and metastasis in breast cancer, thus emerging as a promising target for novel therapies. To identify novel stemness regulators that could potentially be targeted in luminal ER+ tumors, we performed RNA-sequencing (RNA-seq) in MCF-7 adherent monolayer cells and tumorspheres enriched in breast CSCs (bCSCs). We identified 1421 differentially expressed genes (DEGs), with 923 of them being upregulated and 498 downregulated in tumorspheres. Gene ontology and pathway enrichment analyses revealed that distinct gene networks underlie the biology of the two cell systems. We selected the transient receptor potential cation channel subfamily M member 4 (TRPM4) gene that had not been associated with cancer stemness before for further investigation. We confirmed that TRPM4 was overexpressed in tumorspheres and showed that its knock-down affected the stemness properties of bCSCs in vitro. TRPM4 inhibition revealed potential anti-tumor effects by directly targeting the bCSC subpopulation. We suggest that TRPM4 plays a key role in stemness mediation, and its inhibition may represent a novel therapeutic modality against bCSCs contributing in the improvement of breast cancer treatments.

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Section: Trpm4 Regulates the Stemness Properties Of Bcscs In Vitromentioning

confidence: 99%

Transcriptional Profiling of Tumorspheres Reveals TRPM4 as a Novel Stemness Regulator in Breast Cancer

et al. 2021

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“…The aggressive cancer cells usually have the enhanced potential in self-renewal ability, resulting in tumor progression. STAT3 is considered to have an important regulatory effect on the behavior of cancer stem-like cells [ 51 ]. By binding to the promoters of Oct4 , Nanog , and Sox2 , STAT3 could regulate the gene expression of some cancer stem-like cell markers, which may contribute to carcinogenesis and progression [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

MSC-Derived Extracellular Vesicle-Delivered L-PGDS Inhibit Gastric Cancer Progression by Suppressing Cancer Cell Stemness and STAT3 Phosphorylation

You

Jin

Zhang

et al. 2022

Stem Cells International

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Mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) serving as delivery system have attracted extensive research interest, especially in cancer therapy. In our previous study, lipocalin-type prostaglandin D2 synthase (L-PGDS) showed inhibitory effects on gastric cancer growth. In this study, we aimed to explore whether MSC-EV-delivered L-PGDS (EVs-L-PGDS) could inhibit gastric cancer progression. EVs-L-PGDS were generated from MSCs transfected with adenovirus encoding L-PGDS. Cell colony-forming, migration, invasion, and flow cytometry assays were used to show the inhibitory effects of EVs on tumor cells in vitro, and the nude mouse subcutaneous tumor model was performed to show the inhibitory effect of EVs on tumor progression in vivo. In vitro, EVs-L-PGDS could be internalized and inhibit the colony-forming, migration, and invasion ability of gastric cancer cell SGC-7901 and promote cell apoptosis. In vivo, EVs-L-PGDS inhibited the tumor growth in nude mouse subcutaneous tumor-bearing model. Compared with the PBS and EVs containing empty vector (EVs-Vector) group, more apoptotic cells and higher L-PGDS expression were detected in tumor tissue of the EVs-L-PGDS treatment group. And these differences are significant. Mechanistically, EVs-L-PGDS reduced the expression of stem cell markers including Oct4, Nanog, and Sox2 and inhibited STAT3 phosphorylation in gastric cancer cell SGC-7901. In conclusion, our results imply that MSC-derived EVs could be utilized as an effective nanovehicle to deliver L-PGDS for gastric cancer treatment, which provides a novel idea for the EV-based cancer therapy.

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“…EMT is an important process of transdifferentiation in solid cancers progression and the development of metastasis. During EMT polarized, immotile epithelial cells are transformed into migratory mesenchymal-like cells prone to migration, metastasis formation, drug resistance, and BC stemness features development [ 70 , 71 , 72 , 73 ]. Numerous signaling pathways are involved in the EMT process, including: cadherin [ 74 ], notch [ 75 ], transforming growth factor-β (TGF-β) [ 76 ], matrix metalloproteinases [ 77 ], urokinase plasminogen activator [ 78 ] and WNT/beta-catenin [ 79 , 80 ] pathways [ 70 ].…”

Section: Valproic Acid and Breast Cancermentioning

confidence: 99%

Valproic Acid and Breast Cancer: State of the Art in 2021

Wawruszak

Hałasa

Okon

et al. 2021

Cancers

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Valproic acid (2-propylpentanoic acid, VPA) is a short-chain fatty acid, a member of the group of histone deacetylase inhibitors (HDIs). VPA has been successfully used in the treatment of epilepsy, bipolar disorders, and schizophrenia for over 50 years. Numerous in vitro and in vivo pre-clinical studies suggest that this well-known anticonvulsant drug significantly inhibits cancer cell proliferation by modulating multiple signaling pathways. Breast cancer (BC) is the most common malignancy affecting women worldwide. Despite significant progress in the treatment of BC, serious adverse effects, high toxicity to normal cells, and the occurrence of multi-drug resistance (MDR) still limit the effective therapy of BC patients. Thus, new agents which improve the effectiveness of currently used methods, decrease the emergence of MDR, and increase disease-free survival are highly needed. This review focuses on in vitro and in vivo experimental data on VPA, applied individually or in combination with other anti-cancer agents, in the treatment of different histological subtypes of BC.

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Signaling pathways governing breast cancer stem cells behavior

Cited by 78 publications

References 170 publications

Transcriptional Profiling of Tumorspheres Reveals TRPM4 as a Novel Stemness Regulator in Breast Cancer

Transcriptional Profiling of Tumorspheres Reveals TRPM4 as a Novel Stemness Regulator in Breast Cancer

MSC-Derived Extracellular Vesicle-Delivered L-PGDS Inhibit Gastric Cancer Progression by Suppressing Cancer Cell Stemness and STAT3 Phosphorylation

Valproic Acid and Breast Cancer: State of the Art in 2021

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