Salinomycin induces expression of ER and Golgi apparatus related genes in EMT cell model
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ABSTRACT:
PROVIDER: PRJNA514730 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8435270_1.fastq.gz | Fastqsanger.gz | |||
| SRR8435270_2.fastq.gz | Fastqsanger.gz | |||
| SRR8435280_1.fastq.gz | Fastqsanger.gz | |||
| SRR8435280_2.fastq.gz | Fastqsanger.gz | |||
| SRR8435290_1.fastq.gz | Fastqsanger.gz |
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Project description:Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs) that drive tumor metastasis. Recently, a screening of a large compound library on a breast EMT model has identified salinomycin, a K+/H+ ionophore, as a highly selective drug towards CSCs. We used the same EMT model to show that salinomycin targets Golgi apparatus. We have performed RNA-seq analysis on HMLE-Twist and HMLE-pBp cells (EMT and non-EMT) that were either mock treated or treated for 24h with micro molar concentration (0.2uM) of salinomycin. Salinomycin induced expression of genes enriched by known ER and Golgi stressors.
2023-01-11 | GSE124975 | GEO
Project description:Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We show that salinomycin is able to decrease cell viability and induce apoptosis. In combination with the chemotherapeutic agents cisplatin and paclitaxel, salinomycin synergistically killed HNSCC cancer stem cells more effectively than either drug alone. Furthermore, we observed that salinomycin decreases stem cell properties as shown by a significant reduction in sphere formation and a decrease of both CD44 and BMI-1. Contrary to expectations, salinomycin caused an induction of EMT as shown by an increase in Snail and Vimentin, and a decrease in E-cadherin expression. Even though EMT was induced, salinomycin caused a decrease in invasion through a membrane. In search of a possible mechanism, the effects on the Akt pathway were explored. Interestingly, salinomycin also induced phosphorylation of Akt. Activation of EMT and Akt are both tightly associated with an increase in stemness, which brings to question the relationship between CSCs and these two fundamental pathways. Taken together, our findings indicate that salinomycin shows promise as a novel treatment for HNSCC despite an activation of EMT and Akt. MicroRNA obtained from JLO-1 cells treated for 48 hours in varying doses of salinomycin. Changes in microRNA expression are analyzed by normalizing expression values with the control sample.
2013-12-31 | E-GEOD-33196 | biostudies-arrayexpress
Project description:Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We show that salinomycin is able to decrease cell viability and induce apoptosis. In combination with the chemotherapeutic agents cisplatin and paclitaxel, salinomycin synergistically killed HNSCC cancer stem cells more effectively than either drug alone. Furthermore, we observed that salinomycin decreases stem cell properties as shown by a significant reduction in sphere formation and a decrease of both CD44 and BMI-1. Contrary to expectations, salinomycin caused an induction of EMT as shown by an increase in Snail and Vimentin, and a decrease in E-cadherin expression. Even though EMT was induced, salinomycin caused a decrease in invasion through a membrane. In search of a possible mechanism, the effects on the Akt pathway were explored. Interestingly, salinomycin also induced phosphorylation of Akt. Activation of EMT and Akt are both tightly associated with an increase in stemness, which brings to question the relationship between CSCs and these two fundamental pathways. Taken together, our findings indicate that salinomycin shows promise as a novel treatment for HNSCC despite an activation of EMT and Akt.
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Project description:The cumulative role of cellular organelle’s in shaping the life and function of a cell has been long acknowledged. While each organelle plays a specific role in the growth and development of T cells, numerous studies have thus far focused on targeting mitochondria, endoplasmic reticulum, or lysosome related pathways to improve anti-tumor T cell immune response. Here we highlight the tumor microenvironment (TME) mediated disruption of Golgi architecture and function, termed Golgi stress, contributes to altered redox signaling and affects cell survival. Importantly, the decreased expression if GM130, a marker of Golgi stress and indicating the disruption of Golgi architecture, was reverted upon treatment with hydrogen sulphide (H2S) donor GYY4137, or over expressing cystathionine β-synthase (Cbs), an enzyme involved in biosynthesis of endogenous H2S. Activation and expansion of tumor reactive TCR or chimeric antigen receptor bearing T cells expanded with exogenous H2S promoted stemness, antioxidant capacity and exhibited an increase effector cytokine secretion that correlated to increased protein translation. In in vivo models of melanoma and lymphoma, anti-tumor T cells conditioned ex vivo with exogenous H2S or overexpressing Cbs demonstrated superior tumor control upon ACT. Further, sorting anti- tumor T cells based on Golgi structure and abundance resulted in identification of a Golgihi subset of T cells with a unique metabolic signature, superior fitness, and enhanced anti-tumor capacity. These data suggest that H2S can be used an immunomodulatory agent to enhance the efficacy of ACT, and that the structure and function of the Golgi apparatus is an important feature of T cells that determines their anti-tumor capacity.
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