ArticleCell death & disease2022
xCT contributes to colorectal cancer tumorigenesis through upregulation of the MELK oncogene and activation of the AKT/mTOR cascade.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Experimental Detection Methods and Clinical Translational Challenges of Disulfidptosis in Cancer.Cells · 2026Review
- ACSS2 Suppresses Ferroptosis to Drive Breast Cancer Brain Metastasis.Cancer research · 2026Article
- Phosphosite-specific co-regulation networks of MELK kinase: insights from integrative global phosphoproteomes.Journal, genetic engineering & biotechnology · 2026Article
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- The Dual Role of SLC7A11 in Colorectal Cancer Ferroptosis: From Molecular Mechanisms to Therapeutic Opportunities.OncoTargets and therapy · 2026Review
- O-GlcNAcylation of SPOP regulates colorectal cancer progression and ferroptosis by mediating β-catenin degradation.Cell death discovery · 2025Article
- METTL14 induces ferroptosis to inhibit colorectal cancer progression by inhibiting TRIB3 via an m6A-YTHDF2-dependent manner.Journal of molecular histology · 2025Article
- Trifluridine/tipiracil induces ferroptosis by targeting p53 via the p53-SLC7A11 axis in colorectal cancer 3D organoids.Cell death & disease · 2025Article
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies.Military Medical Research · 2025Article
- Exploratory research on therapeutic agents combined with early diagnostic biomarkers for colorectal cancer.Frontiers in pharmacology · 2025Article
- Unveiling the Cuproptosis in Colitis and Colitis-Related Carcinogenesis: A Multifaceted Player and Immune Moderator.Research (Washington, D.C.) · 2025Review
- Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.Molecular cancer · 2024Article
- SLC7A11 promotes EMT and metastasis in invasive pituitary neuroendocrine tumors by activating the PI3K/AKT signaling pathway.Endocrine connections · 2024Article
- A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases.Frontiers in oncology · 2024Article
- MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function.Cell death & disease · 2023Article
- Glutamine metabolism in tumor metastasis: Genes, mechanisms and the therapeutic targets.Heliyon · 2023Review
- Integrated bioinformatics analysis and experimental validation reveals hub genes of rheumatoid arthritis.Experimental and therapeutic medicine · 2023Article
- Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- miR-21-5p Inhibits Ferroptosis in Hepatocellular Carcinoma Cells by Regulating the AKT/mTOR Signaling Pathway through MELK.Journal of immunology research · 2023Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed and deadly malignant tumors globally, and its occurrence and progression are closely related to the poor histological features and complex molecular characteristics among patients. It is urgent to identify specific biomarkers for effective treatment of CRC. In this study, we performed comprehensive experiments to validate the role of xCT expression in CRC tumorigenesis and stemness and confirmed xCT knockdown significantly suppressed the proliferation, migration, and stemness of CRC cells in vitro and effectively inhibited CRC tumorigenesis and metastasis in vivo. In addition, bioinformatic analysis and luciferase assays were used to identify E2F1 as a critical upstream transcription factor of SLC7A11 (the gene encoding for xCT) that facilitated CRC progression and cell stemness. Subsequent RNA sequencing, western blotting, rescue assay, and immunofluorescence assays revealed MELK directly co-expressed with xCT in CRC cells, and its upregulation significantly attenuated E2F1/xCT-mediated tumorigenesis and stemness in CRC. Further molecular mechanism exploration confirmed that xCT knockdown may exert an antitumor effect by controlling the activation of MELK-mediated Akt/mTOR signaling. Erastin, a specific inhibitor of xCT, was also proven to effectively inhibit CRC tumorigenesis and cell stemness. Altogether, our study showed that E2F1/xCT is a promising therapeutic target of CRC that promotes tumorigenesis and cell stemness. Erastin is also an effective antitumoral agent for CRC.
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