Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation

Li, Yu; Zhou, Shuling; Hu, Qiao-ling; Chen, Xueling; Gu, Jiang

doi:10.1038/s41598-020-60903-9

Cited by 16 publications

(9 citation statements)

References 42 publications

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“…We observed a dose- and time-dependent component of ChREBPβ-mediated β-cell death in vivo, FACs-sorted human β-cells from T2D donors displayed a higher ChREBPβ:ChREBPα ratio than from non-diabetic donors, and increasing the ChREBPα abundance mitigated ChREBP-β-mediated cell death in vitro and in vitro in both rodent and human β-cells. These results are in concert with studies showing high levels of ChREBP correlate with poor diagnosis and increased rates of proliferation in certain forms of cancer 48 . Indeed, in many respects, ChREBPβ behaves very much like Myc in β-cells.…”

Section: Discussionsupporting

confidence: 83%

Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure

et al. 2022

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Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell “glucolipotoxicity” can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is mitigated by overexpression of the alternate CHREBP gene product, ChREBPα, or by activation of the antioxidant Nrf2 pathway in rodent and human β-cells. We conclude that ChREBPβ, whether adaptive or maladaptive, is an important determinant of β-cell fate and a potential target for the preservation of β-cell mass in diabetes.

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Section: Discussionsupporting

confidence: 83%

Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure

et al. 2022

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“…This upregulation is caused by gene amplification and DNA hypomethylation and occurs in concert with a cohort of neighboring genes on chromosome locus 20q [ 55 ]. Studies have shown that ChREBP mRNA and protein expression levels are significantly increased in colon cancer tissues compared to normal tissues [ 56 ]. Their expression positively correlated with colon malignancy and was suggested to contribute to cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

Modular and mechanistic changes across stages of colorectal cancer

et al. 2022

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Background While mechanisms contributing to the progression and metastasis of colorectal cancer (CRC) are well studied, cancer stage-specific mechanisms have been less comprehensively explored. This is the focus of this manuscript. Methods Using previously published data for CRC (Gene Expression Omnibus ID GSE21510), we identified differentially expressed genes (DEGs) across four stages of the disease. We then generated unweighted and weighted correlation networks for each of the stages. Communities within these networks were detected using the Louvain algorithm and topologically and functionally compared across stages using the normalized mutual information (NMI) metric and pathway enrichment analysis, respectively. We also used Short Time-series Expression Miner (STEM) algorithm to detect potential biomarkers having a role in CRC. Results Sixteen Thousand Sixty Two DEGs were identified between various stages (p-value ≤ 0.05). Comparing communities of different stages revealed that neighboring stages were more similar to each other than non-neighboring stages, at both topological and functional levels. A functional analysis of 24 cancer-related pathways indicated that several signaling pathways were enriched across all stages. However, the stage-unique networks were distinctly enriched only for a subset of these 24 pathways (e.g., MAPK signaling pathway in stages I-III and Notch signaling pathway in stages III and IV). We identified potential biomarkers, including HOXB8 and WNT2 with increasing, and MTUS1 and SFRP2 with decreasing trends from stages I to IV. Extracting subnetworks of 10 cancer-relevant genes and their interacting first neighbors (162 genes in total) revealed that the connectivity patterns for these genes were different across stages. For example, BRAF and CDK4, members of the Ser/Thr kinase, up-regulated in cancer, displayed changing connectivity patterns from stages I to IV. Conclusions Here, we report molecular and modular networks for various stages of CRC, providing a pseudo-temporal view of the mechanistic changes associated with the disease. Our analysis highlighted similarities at both functional and topological levels, across stages. We further identified stage-specific mechanisms and biomarkers potentially contributing to the progression of CRC.

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“…ChREBP knockdown by siRNA significantly inhibits aerobic glycolysis and the synthesis of lipids in colon cancer cells. Additionally, ChREBP knockdown activates p53, induces cell cycle arrest, and reduces colon cancer growth in vivo, indicating an oncogenic function for ChREBP [ 54 , 55 ]. Positive correlations of MLXIPL mRNA with glycolytic and lipogenic genes were also observed in a comprehensive chromatin immunoprecipitation analysis of human HCC and breast cancer.…”

Section: Transcription Factors Leading To Lipid Metabolism Rewiring In Cancermentioning

confidence: 99%

How cancer cells remodel lipid metabolism: strategies targeting transcription factors

2021

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Reprogramming of lipid metabolism has received increasing recognition as a hallmark of cancer cells because lipid dysregulation and the alteration of related enzyme profiles are closely correlated with oncogenic signals and malignant phenotypes, such as metastasis and therapeutic resistance. In this review, we describe recent findings that support the importance of lipids, as well as the transcription factors involved in cancer lipid metabolism. With recent advances in transcription factor analysis, including computer-modeling techniques, transcription factors are emerging as central players in cancer biology. Considering the limited number and the crucial role of transcription factors associated with lipid rewiring in cancers, transcription factor targeting is a promising potential strategy for cancer therapy.

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Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation

Cited by 16 publications

References 42 publications

Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure

Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure

Modular and mechanistic changes across stages of colorectal cancer

How cancer cells remodel lipid metabolism: strategies targeting transcription factors

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