Acquired drug resistance interferes with the susceptibility of prostate cancer cells to metabolic stress

Catapano, Jessica; Luty, Marcin; Wróbel, Tomasz; Pudełek, Maciej; Piwowarczyk, Katarzyna; Kędracka–Krok, Sylwia; Siedlar, Maciej; Madeja, Zbigniew; Czyż, Jarosław

doi:10.1186/s11658-022-00400-1

Cited by 4 publications

(1 citation statement)

References 56 publications

(79 reference statements)

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“…Thus, the cells in CL2 are undergoing a process of dedifferentiation from being epithelial cells and activating the mesenchymal gene networks. Existing studies have reported that adaptive resistance is positively correlated with the acquisition of mesenchymal traits in cancer 74,75 . CL2 was enriched with signatures associated with metastasis and drug resistance.…”

Section: Scellbow Enables Pseudo-grading Of Metastatic Prostate Cance...mentioning

confidence: 99%

Pseudo-grading of tumor subpopulations from single-cell transcriptomic data using Phenotype Algebra

Sengupta

Nelson

Bhattacharya

et al. 2022

Preprint

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Robust characterization of cellular phenotypes from single-cell gene expression data is of paramount importance in understanding complex biological systems and diseases. Single-cell RNA-seq (scRNA-seq) datasets are inherently noisy due to small amounts of starting RNA. Over the last few years, several methods have been developed to make single-cell analysis fast and efficient. Most of these methods are based on statistical and machine learning principles. In the current work, we describe SCellBOW, which encodes single-cell expression vectors as documents, thereby enabling the application of powerful language models. Beyond the identification of robust cell type clusters, our algorithm provides a latent representation of single-cells in a manner that captures the ‘semantics’ associated with cellular phenotypes. These representations,akaembeddings, allow algebraic operations such as ‘+’ and ‘-’. We use this hitherto unexplored utility to stratify cancer clones in terms of their aggressiveness and contribution to disease prognosis. Further, the application of SCellBOW to a scRNA-seq dataset comprising human splenocytes and matched peripheral blood mononuclear cells (∼5000 cells) identifies unknown cell states that bear significance in advancing our understanding of spleen biology.

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Section: Scellbow Enables Pseudo-grading Of Metastatic Prostate Cance...mentioning

confidence: 99%

Pseudo-grading of tumor subpopulations from single-cell transcriptomic data using Phenotype Algebra

Sengupta

Nelson

Bhattacharya

et al. 2022

Preprint

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Cancer immunometabolism: advent, challenges, and perspective

Dang,

Li,

Jin

et al. 2024

Mol Cancer

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For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

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Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress

Pudełek,

Ryszawy,

Piwowarczyk

et al. 2024

J Transl Med

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Background Multi-drug resistance of poly(morpho)nuclear giant cells (PGCs) determines their cytoprotective and generative potential in cancer ecosystems. However, mechanisms underlying the involvement of PGCs in glioblastoma multiforme (GBM) adaptation to chemotherapeutic regimes remain largely obscure. In particular, metabolic reprogramming of PGCs has not yet been considered in terms of GBM recovery from doxorubicin (DOX)-induced stress. Methods Long-term proteomic and metabolic cell profiling was applied to trace the phenotypic dynamics of GBM populations subjected to pulse DOX treatment in vitro, with a particular focus on PGC formation and its metabolic background. The links between metabolic reprogramming, drug resistance and drug retention capacity of PGCs were assessed, along with their significance for GBM recovery from DOX-induced stress. Results Pulse DOX treatment triggered the transient formation of PGCs, followed by the appearance of small expanding cell (SEC) clusters. Development of PGCs was accompanied by the mobilization of their metabolic proteome, transient induction of oxidative phosphorylation (OXPHOS), and differential intracellular accumulation of NADH, NADPH, and ATP. The metabolic background of PGC formation was confirmed by the attenuation of GBM recovery from DOX-induced stress following the chemical inhibition of GSK-3β, OXPHOS, and the pentose phosphate pathway. Concurrently, the mobilization of reactive oxygen species (ROS) scavenging systems and fine-tuning of NADPH-dependent ROS production systems in PGCs was observed. These processes were accompanied by perinuclear mobilization of ABCB1 and ABCG2 transporters and DOX retention in the perinuclear PGC compartments. Conclusions These data demonstrate the cooperative pattern of GBM recovery from DOX-induced stress and the crucial role of metabolic reprogramming of PGCs in this process. Metabolic reprogramming enhances the efficiency of self-defense systems and increases the DOX retention capacity of PGCs, potentially reducing DOX bioavailability in the proximity of SECs. Consequently, the modulation of PGC metabolism is highlighted as a potential target for intervention in glioblastoma treatment.

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Acquired drug resistance interferes with the susceptibility of prostate cancer cells to metabolic stress

Cited by 4 publications

References 56 publications

Pseudo-grading of tumor subpopulations from single-cell transcriptomic data using Phenotype Algebra

Pseudo-grading of tumor subpopulations from single-cell transcriptomic data using Phenotype Algebra

Cancer immunometabolism: advent, challenges, and perspective

Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress

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