ArticleJournal of cellular and molecular medicine2021
Targeting hexokinase 2 increases the sensitivity of oxaliplatin by Twist1 in colorectal cancer.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Multi-omics integration in deciphering non-small cell lung cancer drug resistance: current status, challenges, and future prospects.Hereditas · 2026Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Oxaliplatin and 5-fluorouracil promote epithelial-mesenchymal transition via activation of KRAS/ERK/NF-κB pathway in KRAS-mutated colon cancer cells.Molecular and cellular biochemistry · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- Glucose Metabolism and Tumor Microenvironment: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- TWIST1 regulates HK2 ubiquitination degradation to promote pancreatic cancer invasion and metastasis.Cancer cell international · 2025Article
- A novel USP4 inhibitor that suppresses colorectal cancer stemness by promoting β-catenin and Twist1 degradation.Journal of translational medicine · 2025Article
- Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.Current pharmaceutical design · 2025Review
- The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors.Cell communication and signaling : CCS · 2024Review
- Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance.Translational oncology · 2024Review
- LncRNAAsian journal of urology · 2024Article
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- Oncogenic Alterations of Metabolism Associated with Resistance to Chemotherapy.Current molecular medicine · 2024Review
- Novel chromium (III)-based compound for inhibition of oxaliplatin-resistant colorectal cancer progression.American journal of cancer research · 2024Article
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.International journal of molecular sciences · 2023Review
- Down-regulated FTO and ALKBH5 co-operatively activates FOXO signaling through m6A methylation modification in HK2 mRNA mediated by IGF2BP2 to enhance glycolysis in colorectal cancer.Cell & bioscience · 2023Article
- Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis.Cancer biology & medicine · 2022Article
- Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4.Journal of cellular and molecular medicine · 2022Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is the third most malignant tumour worldwide, with high mortality and recurrence. Chemoresistance is one of the main factors leading to metastasis and poor prognosis in advanced CRC patients. By analysing the Gene Expression Omnibus data set, we found higher hexokinase 2 (HK2) expression levels in patients with metastatic CRC than in those with primary CRC. Moreover, we observed higher enrichment in oxaliplatin resistance-related gene sets in metastatic CRC than in primary CRC. However, the underlying relationship has not yet been elucidated. In our study, HK2 expression was significantly elevated in CRC patients. Gene set enrichment analysis (GSEA) revealed multi-drug resistance and epithelial-mesenchymal transition (EMT) pathways related to high HK2 expression. Our results showed that knockdown of HK2 significantly inhibited vimentin and Twist1 expression and promoted TJP1 and E-cadherin expression in CRC cells. Additionally, transcriptional and enzymatic inhibition of HK2 by 3-bromopyruvate (3-bp) impaired oxaliplatin resistance in vitro and in vivo. Mechanistically, HK2 interacts with and stabilized Twist1 by preventing its ubiquitin-mediated degradation, which is related to oxaliplatin resistance, in CRC cells. Overexpression of Twist1 reduced the apoptosis rate by HK2 knockdown in CRC cells. Collectively, we discovered that HK2 is a crucial regulator that mediates oxaliplatin resistance through Twist1. These findings identify HK2 and Twist1 as promising drug targets for CRC chemoresistance.
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