Centromere protein A (CENPA) regulates metabolic reprogramming in the colon cancer cells by transcriptionally activating karyopherin subunit alpha 2 (KPNA2)

2021 ◽  
Author(s):  
Yi-Chao Liang ◽  
Qi Su ◽  
Yu-Jie Liu ◽  
Hong Xiao ◽  
Hong-Zhuan Yin
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Protein A ◽  
Metabolic Reprogramming ◽  
Colon Cancer Cells ◽  
Centromere Protein ◽  
Centromere Protein A

scholarly journals Metabolism-Based Molecular Sub-Phenotyping Predict Ketogenic Diet Responses in Colorectal Cancer

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 356-356
Author(s):  
Meng Tang ◽  
Qi Zhang ◽  
Kangping Zhang ◽  
Xi Zhang ◽  
Hanping Shi
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ketogenic Diet ◽  
Theoretical Basis ◽  
Nutritional Stress ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Colon Cancer Cells ◽  
Metabolic Heterogeneity

Abstract Objectives Current studies have confirmed that the sensitivity of the ketogenic diet (KD) therapy for cancer depends on the low expression of ketolytic enzymes. However, increasing evidence showed that heterogeneity of tumor metabolism leads to inconsistent efficacies of KD therapy, which broke the illusion of the possibility of cancer treatment. Our study aims to construct colon cancer metabolism-related molecular subtyping. Furthermore, to explore the metabolic heterogeneity in diverse colon cancer cells and illuminate the mechanisms of mitochondrial metabolic reprogramming. Thus, providing a theoretical basis for clinical nutritional therapy and combined intervention measures based on metabolic molecular phenotyping. Methods We selected 19 genes associated with glucose and the keto-body metabolic pathway, then constructed a prognostic gene signature by LASSO and KM curve.  Based on the screened metabolic molecules, we further explored the nutrition metabolic heterogeneity and illuminate our understanding of mitochondrial metabolic reprogramming under nutritional stress in vivo. Results Through the integration of patients’ transcriptomics data,  we stratified colon cancer patients into three significant phenotypes with distinct glycolytic and ketolytic characteristics. We identified glycolysis + subtype with either GLUT1 or PFKFB3 overexpression, and ketolysis + subtype with either OXCT1 or ACAT1 deficiency.  In general, combining glycolysis+/ketolysis-phenotype demonstrated the worst prognosis. Furthermore, we discovered the metabolic heterogeneity through western blot and energy metabolic phenotype analysis which also confirmed that these different colon cancer cells showed great significance in metabolic reprogramming under nutritional stress. Conclusions The multi-target combination of metabolic phenotyping proved to be a foundation for individualized molecular stratified treatment which plays an essential role in predicting effectiveness of nutritional modulation therapy among colon cancer patients. It provided a theoretical basis for the clinical trial of KD therapy for patients with specific metabolic subtypes of colon cancer. Funding Sources The National Key Research and Development Program: The key technology of palliative care and nursing for cancer patients.

scholarly journals Camptothecin Encapsulated in β-Cyclodextrin-EDTA-Fe3O4 Nanoparticles Induce Metabolic Reprogramming Repair in HT29 Cancer Cells through Epigenetic Modulation: A Bioinformatics Approach

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3163
Author(s):  
Aisha Farhana ◽  
Avin Ee-Hwan Koh ◽  
Pooi Ling Mok ◽  
Abdullah Alsrhani ◽  
Yusuf Saleem Khan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Fe3o4 Nanoparticles ◽  
Epigenetic Modifications ◽  
Metabolic Reprogramming ◽  
Colon Cancer Cells ◽  
Ht29 Cells ◽  
Attractive Therapeutic Target ◽  
Normal Metabolism ◽  
Epigenetic Modulation

Cancer progresses through a distinctive reprogramming of metabolic pathways directed by genetic and epigenetic modifications. The hardwired changes induced by genetic mutations are resilient, while epigenetic modifications are softwired and more vulnerable to therapeutic intervention. Colon cancer is no different. This gives us the need to explore the mechanism as an attractive therapeutic target to combat colon cancer cells. We have previously established the enhanced therapeutic efficacy of a newly formulated camptothecin encapsulated in β-cyclodextrin-EDTA-Fe3O4 nanoparticles (CPT-CEF) in colon cancer cells. We furthered this study by carrying out RNA sequencing (RNA-seq) to underscore specific regulatory signatures in the CPT-CEF treated versus untreated HT29 cells. In the study, we identified 95 upregulated and 146 downregulated genes spanning cellular components and molecular and metabolic functions. We carried out extensive bioinformatics analysis to harness genes potentially involved in epigenetic modulation as either the cause or effect of metabolic rewiring exerted by CPT-CEF. Significant downregulation of 13 genes involved in the epigenetic modulation and 40 genes from core metabolism was identified. Three genes, namely, DNMT-1, POLE3, and PKM-2, were identified as the regulatory overlap between epigenetic drivers and metabolic reprogramming in HT29 cells. Based on our results, we propose a possible mechanism that intercepts the two functional axes, namely epigenetic control, and metabolic modulation via CPT-CEF in colon cancer cells, which could skew cancer-induced metabolic deregulation towards metabolic repair. Thus, the study provides avenues for further validation of transcriptomic changes affected by these deregulated genes at epigenetic level, and ultimately may be harnessed as targets for regenerating normal metabolism in colon cancer with better treatment potential, thereby providing new avenues for colon cancer therapy.

scholarly journals The POU2F1-ALDOA axis promotes the proliferation and chemoresistance of colon cancer cells by enhancing glycolysis and the pentose phosphate pathway activity

Oncogene ◽  
2022 ◽  
Author(s):  
Jinguan Lin ◽  
Longzheng Xia ◽  
Linda Oyang ◽  
Jiaxin Liang ◽  
Shiming Tan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Pentose Phosphate Pathway ◽  
Aerobic Glycolysis ◽  
Human Colon ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Pou Domain

AbstractCancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of POU domain class 2 transcription factor 1 (POU2F1) on metabolic reprogramming in colon cancer. The POU2F1 expression was analyzed in GEO dataset, TCGA cohorts and human colon cancer tissues by bioinformatics and immunohistochemistry. The effects of altered POU2F1 expression on proliferation, glucose metabolism and oxaliplatin sensitivity of colon cancer cells were tested. The impacts of POU2F1 on aldolase A (ALDOA) expression and malignant behaviors of colon cancer cells were examined. We found that up-regulated POU2F1 expression was associated with worse prognosis and oxaliplatin resistance in colon cancer. POU2F1 enhanced the proliferation, aerobic glycolysis and the pentose phosphate pathway (PPP) activity, but reduced oxidative stress and apoptosis in colon cancer cells, dependent on up-regulating ALDOA expression. Mechanistically, POU2F1 directly bound to the ALDOA promoter to enhance the ALDOA promoter activity in colon cancer cells. Moreover, activation of the POU2F1-ALDOA axis decreased the sensitivity to oxaliplatin in colon cancer cells. These data indicate that the POU2F1-ALDOA axis promotes the progression and oxaliplatin resistance by enhancing metabolic reprogramming in colon cancer. Our findings suggest that the POU2F1-ALDOA axis may be new therapeutic targets to overcome oxaliplatin resistance in colon cancer.

Leptin is a growth factor for human colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

Silencing of a death associated protein kinase as a pro-survival factor in colon cancer cells

Endoscopy ◽  
2005 ◽  
Vol 37 (05) ◽  
Author(s):  
GA Doherty ◽  
SM Byrne ◽  
SC Austin ◽  
GM Scully ◽  
EW Kay ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Survival Factor ◽  
Death Associated Protein Kinase

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

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