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 Tumour‐suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model

2020 ◽  
Vol 251 (3) ◽  
pp. 297-309
Author(s):  
Geriolda Topi ◽  
Shakti Ranjan Satapathy ◽  
Pujarini Dash ◽  
Syrina Fred Mehrabi ◽  
Roy Ehrnström ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Oestrogen Receptor ◽  
Suppressive Effect ◽  
Colon Cancer Cells ◽  
Zebrafish Model ◽  
Colorectal 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 role of coagulation and platelets in colon cancer-associated thrombosis

2019 ◽  
Vol 316 (2) ◽  
pp. C264-C273 ◽  
Author(s):  
Annachiara Mitrugno ◽  
Samuel Tassi Yunga ◽  
Joanna L. Sylman ◽  
Jevgenia Zilberman-Rudenko ◽  
Toshiaki Shirai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Cell Interactions ◽  
Coagulation Cascade ◽  
Colon Cancer Cells ◽  
Cancer Associated Thrombosis

Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and thromboxane A2. Platelet-colon cancer cell interactions potentiated the release of platelet-derived extracellular vesicles (EVs) rather than cancer cell-derived EVs. Our data show that single colon cancer cells were capable of recruiting and activating platelets and generating fibrin in plasma under shear flow. Finally, in a retrospective analysis of colon cancer patients, we found that the number of venous thromboembolism events was 4.5 times higher in colon cancer patients than in a control population. In conclusion, our data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients. Our work may provide rationale for targeting platelet-cancer cell interactions with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis, balancing safety with efficacy.

scholarly journals PINCH expression in relation to radiation response in co-cultured colon cancer cells and in rectal cancer patients

2013 ◽  
Vol 30 (5) ◽  
pp. 2097-2104 ◽  
Author(s):  
ANNICA HOLMQVIST ◽  
BIRGITTA HOLMLUND ◽  
MALIN ARDSBY ◽  
SURAJIT PATHAK ◽  
XIAO-FENG SUN
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Radiation Response ◽  
Colon Cancer Cells

scholarly journals Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity

Oncogenesis ◽  
2021 ◽  
Vol 10 (11) ◽  
Author(s):  
Rida Iftikhar ◽  
Harrison M. Penrose ◽  
Angelle N. King ◽  
Joshua S. Samudre ◽  
Morgan E. Collins ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Increased Risk

AbstractObesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role of adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LD) utilization, in obesity-driven colonic tumorigenesis. In local colon cancer patients, significantly increased ATGL levels in tumor tissue, compared to controls, were augmented in obese individuals. Elevated ATGL levels in human colon cancer cells (CCC) relative to non-transformed were augmented by an obesity mediator, oleic acid (OA). In CCC and colonospheres, enriched in colon cancer stem cells (CCSC), inhibition of ATGL prevented LDs utilization and inhibited OA-stimulated growth through retinoblastoma-mediated cell cycle arrest. Further, transcriptomic analysis of CCC, with inhibited ATGL, revealed targeted pathways driving tumorigenesis, and high-fat-diet obesity facilitated tumorigenic pathways. Inhibition of ATGL in colonospheres revealed targeted pathways in human colonic tumor crypt base cells (enriched in CCSC) derived from colon cancer patients. In CCC and colonospheres, we validated selected transcripts targeted by ATGL inhibition, some with emerging roles in colonic tumorigeneses (ATG2B, PCK2, PGAM1, SPTLC2, IGFBP1, and ABCC3) and others with established roles (MYC and MUC2). These findings demonstrate obesity-promoted, ATGL-mediated colonic tumorigenesis and establish the therapeutic significance of ATGL in obesity-reinforced colon cancer progression.

Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells

2012 ◽  
Vol 27 (11) ◽  
pp. 1401-1408 ◽  
Author(s):  
Petra Faltejskova ◽  
Andrej Besse ◽  
Sabina Sevcikova ◽  
Lenka Kubiczkova ◽  
Marek Svoboda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Colon Cancer Cells ◽  
Clinical Correlations ◽  
Colorectal Cancer Patients

scholarly journals AURKA Increase the Chemosensitivity of Colon Cancer Cells to Oxaliplatin by Inhibiting the TP53-Mediated DNA Damage Response Genes

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Baocong Shan ◽  
Ran Zhao ◽  
Jian Zhou ◽  
Minghui Zhang ◽  
Xiaoyu Qi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Dna Damage Response ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Expression Change ◽  
Damage Response ◽  
Cancer Types

AURKA, a cell cycle-regulated kinase, is associated with malignant transformation and progression in many cancer types. We analyzed the expression change of AURKA in pan-cancer and its effect on the prognosis of cancer patients using the TCGA dataset. We revealed that AURKA was extensively elevated and predicted a poor prognosis in most of the detected cancer types, with an exception in colon cancer. AURKA was elevated in colon cancer, but the upregulation of AURKA indicated better outcomes of colon cancer patients. Then we revealed that undermethylation of the AURKA gene and several transcription factors contributed to the upregulation of AURKA in colon cancer. Moreover, we demonstrated that AURKA overexpression promoted the death of colon cancer cells induced by Oxaliplatin, whereas knockdown of AURKA significantly weakened the chemosensitivity of colon cancer cells to Oxaliplatin. Mechanistically, AURKA inhibited DNA damage response by suppressing the expression of various DNA damage repair genes in a TP53-dependent manner, which can partly explain that ARUKA is associated with a beneficial outcome of colon cancer. This study provided a possibility to use AURKA as a biomarker to predict the chemosensitivity of colon cancer to platinum in the clinic.

scholarly journals Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

2018 ◽  
Vol 19 (8) ◽  
pp. 2427 ◽  
Author(s):  
Ya-Ling Hsu ◽  
Yi-Jen Chen ◽  
Wei-An Chang ◽  
Shu-Fang Jian ◽  
Hsiao-Li Fan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Critical Factor ◽  
Prognostic Impact ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Cxcl1 Expression

Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression.

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.

Sign in / Sign up

Export Citation Format

Share Document