Polyamines and related signaling pathways in cancer

Li, Jiajing; Meng, Yan; Wu, Xiaolin; Sun, Yuxin

doi:10.1186/s12935-020-01545-9

Cited by 89 publications

(71 citation statements)

References 94 publications

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“…We also found a possible higher potential to produce polyamines mainly due to the increased prevalence of E. coli in the guts of patients with PDAC. Dysregulated polyamine levels have been associated with toxic effects and carcinogenesis, and increased polyamine levels in urine and blood specimens have been found among other cancers, such as skin cancer [ 41 ]. However, we failed to measure polyamines in our subjects, whether there is a relationship between polyamines and PDAC needs further study.…”

Section: Discussionmentioning

confidence: 99%

The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing

Zhou

et al. 2021

J Transl Med

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Background The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal microbiota in patients with PDAC and AIP, and explore the possibility of fecal microbial biomarkers for distinguishing PDAC and AIP. Methods 32 patients with PDAC, 32 patients with AIP and 32 age- and sex-matched healthy controls (HC) were recruited and the fecal microbiotas were analyzed through high-throughput metagenomic sequencing. Alterations of fecal short-chain fatty acids were measured using gas chromatographic method. Results Principal coordinate analysis (PCoA) revealed that microbial compositions differed significantly between PDAC and HC samples; whereas, AIP and HC individuals tended to cluster together. Significant reduction of phylum Firmicutes (especially butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis) and significant increase of phylum Proteobacteria (especially Gammaproteobacteria) were observed only among PDAC samples. At species level, when compared with HC samples, we revealed 24 and 12 differently enriched bacteria in PDAC and AIP, respectively. Functional analysis showed a depletion of short-chain fatty acids synthesis associated KO modules (e.g. Wood-Ljungdahl pathway) and an increase of KO modules associated with bacterial virulence (e.g. type II general secretion pathway). Consistent with the downregulation of butyrate-producing bacteria, gas chromatographic analysis showed fecal butyrate content was significantly decreased in PDAC group. Eubacterium rectale, Eubacterium ventrisum and Odoribacter splanchnicus were among the most important biomarkers in distinguishing PDAC from HC and from AIP individuals. Receiver Operating Characteristic analysis showed areas under the curve of 90.74% (95% confidence interval [CI] 86.47–100%), 88.89% (95% CI 73.49–100%), and 76.54% (95% CI 52.5–100%) for PDAC/HC, PDAC/AIP and AIP/HC, respectively. Conclusions In conclusion, alterations in fecal microbiota and butyrate of patients with PDAC suggest an underlying role of gut microbiota for the pathogenesis of PDAC. Fecal microbial and butyrate as potential biomarkers may facilitate to distinguish patients with PDAC from patients with AIP and HCs which worth further validation.

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Section: Discussionmentioning

confidence: 99%

The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing

Zhou

et al. 2021

J Transl Med

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“…Several works have demonstrated that PAs have antioxidative effects [10], can promote homology-directed DNA repair [11], and downregulate DNA damage-associated cell death [12,13]. Almost all cells can produce PAs, but their production is especially high in rapidly growing cells; therefore, the concentration of PAs as well as the gene expression and activity of enzymes involved in PA biosynthesis are higher in cancer tissues than in normal surrounding tissues [14][15][16]. Therefore, the pathway of PA metabolism is a promising target for chemotherapy and chemoprevention [17].…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes

Gladilina

Bey

Hilal

et al. 2022

IJMS

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Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan, leading to an increase in cell survival and viability. The induction of RAD51A expression was in response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and cancer cells to polyamines may become the basis for the use of these compounds to protect normal lymphocytes during lymphoblastic chemotherapy.

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“…We argue that at least 3 strong roles of glutamine exist in prostate and/or prostate cancers. First, the most prominent function of the prostate is to produce and secrete polyamines, especially spermine, a major component of prostatic fluid, which functions to protect sperm DNA for safe fertilization (Affronti et al., 2020; Li et al., 2020). Glutamine can be metabolized to ornithine by two enzymes, glutaminase (GLS) and ornithine amino transferase (OAT), sequentially, and then ornithine is metabolized to polyamines.…”

Section: Discussionmentioning

confidence: 99%

VCP relocalization limits mitochondrial activity, GSH depletion and ferroptosis during starvation in PC3 prostate cancer cells

et al. 2021

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During periods of crisis, cells must compensate to survive. To this end, cells may need to alter the subcellular localization of crucial proteins. Here, we show that during starvation, VCP, the most abundant soluble ATPase, relocalizes and forms aggregate‐like structures at perinuclear regions in PC3 prostate cancer cells. This movement is associated with a lowered metabolic state, in which mitochondrial activity and ROS production are reduced. VCP appears to explicitly sense glutamine levels, as removal of glutamine from complete medium triggered VCP relocalization and its addition to starvation media blunted VCP relocalization. Cells cultured in Gln(+) starvation media exhibited uniformly distributed VCP in the cytoplasm (free VCP) and underwent ferroptotic cell death, which was associated with a decrease in GSH levels. Moreover, the addition of a VCP inhibitor, CB‐5083, in starvation media prevented VCP relocalization and triggered ferroptotic cell death. Likewise, expression of GFP‐fused VCP proteins, irrespective of ATPase activities, displayed free VCP and triggered cell death during starvation. These results indicate that free VCP is essential for the maintenance of mitochondrial function and that PC3 cells employ a strategy of VCP self‐aggregation to suppress mitochondrial activity in order to escape cell death during starvation, a novel VCP‐mediated survival mechanism.

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Polyamines and related signaling pathways in cancer

Cited by 89 publications

References 94 publications

The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing

The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing

Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes

VCP relocalization limits mitochondrial activity, GSH depletion and ferroptosis during starvation in PC3 prostate cancer cells

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