ArticleEBioMedicine2018
The Circadian Clock Regulates Metabolic Phenotype Rewiring Via HKDC1 and Modulates Tumor Progression and Drug Response in Colorectal Cancer.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Circadian Disruption as a Determinant of the Tumor Temporal State in Colorectal Cancer: A PRISMA-Based Systematic Review Integrating Metabolism, Immunity, and Metastasis.International journal of molecular sciences · 2026Pooled it
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- Oncometabolite signatures from tumor-stroma crosstalk as potential non-invasive biomarkers.Cell death discovery · 2026Article
- Personalized metabolite biomarker predictions reveal heterogeneous characteristics of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Advances in research on circadian rhythms and colorectal cancer.BMC medical genomics · 2026Review
- HNF4α-HKDC1 axis orchestrates a metabolic rewiring to promote migration and metastasis in advanced gastric cancer.Cell death & disease · 2026Article
- The HKDC1-ASS1-ACSBG2 axis reprograms lipid metabolism to drive therapeutic resistance in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Circadian Clock Genes in Colorectal Cancer: From Molecular Mechanisms to Chronotherapeutic Applications.Biomedicines · 2026Review
- Epigenetic reprogramming of hexokinase domain containing 1 (HKDC1) promotes proliferation in colorectal cancer.American journal of cancer research · 2026Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- TCM-Driven Circadian Modulation in Cancer: Engineering Spatiotemporal Drug Delivery for Precision Oncology.International journal of nanomedicine · 2026Review
- Immune Cell-Mediated Retinoblastoma Development: Genetic and Molecular Mechanisms.International journal of genomics · 2026Article
- Circadian rhythm in gastrointestinal cancer: clinical applications and future perspectives.Annals of medicine · 2025Review
- Circadian genesJournal of Zhejiang University. Science. B · 2025Review
- Dysfunction of core clock genes regulates malignant phenotype and gemcitabine sensitivity of cholangiocarcinoma cells.Anti-cancer drugs · 2025Article
- Menin regulates YBX1 nucleus translocation to boost the HKDC1 transcription and affects pancreatic cancer glycolysis.iScience · 2025Article
- Haoya Wang Et Al.: Circadian Rhythm Disruption Promotes Tumor Progression Through Upregulated Glycolysis.Cancer medicine · 2025Review
- Deciphering the circadian rhythm in colorectal cancer: a bibliometric analysis of research landscape and trends.Frontiers in oncology · 2025Article
- HKDC1 in Cancer: Mechanisms, Clinical Applications, and Future.Journal of Cancer · 2025Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An endogenous molecular clockwork drives various cellular pathways including metabolism and the cell cycle. Its dysregulation is able to prompt pathological phenotypes including cancer. Besides dramatic metabolic alterations, cancer cells display severe changes in the clock phenotype with likely consequences in tumor progression and treatment response. In this study, we use a comprehensive systems-driven approach to investigate the effect of clock disruption on metabolic pathways and its impact on drug response in a cellular model of colon cancer progression. We identified distinctive time-related transcriptomic and metabolic features of a primary tumor and its metastatic counterpart. A mapping of the expression data to a comprehensive genome-scale reconstruction of human metabolism allowed for the in-depth functional characterization of 24 h-oscillating transcripts and pointed to a clock-driven metabolic reprogramming in tumorigenesis. In particular, we identified a set of five clock-regulated glycolysis genes, ALDH3A2, ALDOC, HKDC1, PCK2, and PDHB with differential temporal expression patterns. These findings were validated in organoids and in primary fibroblasts isolated from normal colon and colon adenocarcinoma from the same patient. We further identified a reciprocal connection of HKDC1 to the clock in the primary tumor, which is lost in the metastatic cells. Interestingly, a disruption of the core-clock gene BMAL1 impacts on HKDC1 and leads to a time-dependent rewiring of metabolism, namely an increase in glycolytic activity, as well as changes in treatment response. This work provides novel evidence regarding the complex interplay between the circadian clock and metabolic alterations in carcinogenesis and identifies new connections between both systems with pivotal roles in cancer progression and response to therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.