Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression

Guo, Yunlong; Ye, Qing; Deng, Pan; Cao, Yanan; He, Daheng; Zhou, Zhiyong; Wang, Chi; Zaytseva, Yekaterina Y.; Schwartz, Charles E.; Lee, Eun Young; Evers, B. Mark; Morris, Andrew J.; Liu, Side; She, Qing‐Bai

doi:10.1038/s41467-020-17067-x

Cited by 68 publications

(46 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A piece of strong evidence is that the levels of putrescine and agmatine were described to increase with the progression of CRC (38,39). Additionally, Guo et al found the synergistic effect of spermine synthase and oncogene MYC increased polyamine metabolites, suggesting dysregulation of polyamine metabolism has been linked to the development of CRC (40).…”

Section: Other Metabolites and Crcmentioning

confidence: 99%

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

Zhang

Qin

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.

show abstract

Section: Other Metabolites and Crcmentioning

confidence: 99%

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

Zhang

Qin

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…In the future, an inhibitor suitable for clinical use could be developed for TXNRD1 and its combined use with sorafenib might improve the therapeutic effect. SMS, a polyamine biosynthetic enzyme, is overexpressed in patients with colorectal cancer and collaborates with MYC to promote colorectal cancer cell survival ( Guo et al, 2020 ). However, little is known about SMS in liver disease and HCC and more experiments are necessary to reveal its role in HCC.…”

Section: Discussionmentioning

confidence: 99%

Six Metabolism Related mRNAs Predict the Prognosis of Patients With Hepatocellular Carcinoma

Lan

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive solid malignant tumors and current research regards HCC as a type of metabolic disease. This study aims to establish a metabolism-related mRNA signature model for risk assessment and prognosis prediction in HCC patients.Methods: HCC data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) was used to screen out the candidate mRNAs and calculate the risk coefficient to establish the prognosis model. A high-risk group and low-risk group were separated for further study depending on their median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort.Results: A total of 548 differential mRNAs were identified from HCC samples (n = 374) and normal controls (n = 50), 45 of which were correlated with prognosis. A total of 373 samples met the screening criteria and there were randomly divided into the training cohort (n = 186) and the validation cohort (n = 187). In the training cohort, six metabolism-related mRNAs were used to construct a prognostic model with a LASSO regression model. Based on the risk model, the overall survival rate of the high-risk cohort was significantly lower than that of the low-risk cohort. The results of a time-ROC curve proved that the risk score (AUC = 0.849) had a higher prognostic value than the pathological grade, clinical stage, age or gender.Conclusion: The model constructed by the six metabolism-related mRNAs has a significant value for survival prediction and can be applied to guide the evaluation of HCC and the designation of clinical therapy.

show abstract

“…In MCF-7 cell, oestrogen also positively regulates ODC1 gene expression and protein activity [ 7 ]. c-Myc on the other hand positively regulates ODC1 gene expression [ 36 , 37 ] and along with spermine synthase promotes cancer cell survival [ 38 ]. Thus, differences in gene expression patterns together with the hormone receptor status of the cells may contribute to their differential responses to polyamine pathway inhibition and may help predict the sensitivity of breast cancers to polyamine targeting therapy.…”

Section: Discussionmentioning

confidence: 99%

Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Akinyele

Wallace

2021

Biomolecules

View full text Add to dashboard Cite

Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

show abstract

Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression

Cited by 68 publications

References 66 publications

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

Six Metabolism Related mRNAs Predict the Prognosis of Patients With Hepatocellular Carcinoma

Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Contact Info

Product

Resources

About