The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Tanabe, Atsushi; Sahara, Hiroeki

doi:10.3390/cancers12102780

Cited by 39 publications

(35 citation statements)

References 209 publications

(397 reference statements)

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“…C Tumor images and formation rate derived from BGC823 cells with or without SLC7A11 knockdown. D The confidence intervals for 1/(stem cell frequency) was calculated based on the results shown in C. E HE staining images of lung obtained from mice with injection of GC cells with or without miR-375 overexpression reprograming their metabolism to flexibly respond to environmental changes [66]. Thus, we think that SLC7A11 expression in this limited tissue samples might not reflect the correlation between SLC7A11 expression and stemness or metastasis.…”

Section: Discussionmentioning

confidence: 99%

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

et al. 2021

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Background Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness. Methods Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored. Results MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. Conclusion MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.

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Section: Discussionmentioning

confidence: 99%

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

et al. 2021

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“…Thus, L-asparaginase (ASNase) treatment in ALL patients catalyzes the conversion of plasma L-asparagine to aspartic acid and ammonia, leading to the death of cancer cells due to the inhibited global protein synthesis. Similarly, deterioration of asparagine uptake might also cause the death of ALL but not normal cells [ 149 , 150 , 151 , 152 ].…”

Section: Amino Acid Transporters As Targets For Tumor Treatmentmentioning

confidence: 99%

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Kahya

Köseer

Dubrovska

2021

Cancers

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Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

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“…CSCs are cancer cell subpopulations endowed with great adaptive potential which allows them to survive therapy-induced stress and to drive tumor relapse and metastasis, as an effect of molecular adaptive processes fueling clonal rearrangements of cancer cell subpopulations. CSCs are characterized by the expression of stemness genes and detoxifying systems and by great metabolic plasticity [ 144 , 145 , 146 , 147 ]. Epithelial to mesenchymal (EMT) transition is believed to play a role in fueling the emergence of CSC subpopulations [ 148 ].…”

Section: Epha2 Promotes Resistance To Therapymentioning

confidence: 99%

EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?

Cioce

Fazio

2021

Cancers

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The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC); however, what causes EphA2 to switch between tumor-suppressive and tumor-promoting function is still an active theater of investigation. This review summarizes the recent advances in understanding EphA2 function in cancer, with detail on the molecular determinants of the oncogene-tumor suppressor switch function of EphA2. We describe tumor context-specific examples of EphA2 signaling and the emerging role EphA2 plays in supporting cancer—stem—cell-like populations and overcoming therapy-induced stress. In such a frame, we detail the interaction of the EphA2 and EGFR pathway in solid tumors, including colorectal cancer. We discuss the contribution of the EphA2 oncogenic signaling to the resistance to EGFR blocking agents, including cetuximab and TKIs.

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The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Cited by 39 publications

References 209 publications

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?

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