ArticleCells2022
TFEB Regulates ATP7B Expression to Promote Platinum Chemoresistance in Human Ovarian Cancer Cells.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Allelic variation in the ATP7B gene promoter. Implications for phenotype variability, neurodegeneration and Pt resistance in tumor diseases.Journal of human genetics · 2026Article
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- Lys-ing the Resistance: Targeting Lysosomes to Overcome Chemoresistance in Ovarian Cancer.Current oncology reports · 2026Review
- Advancing the frontiers of ovarian cancer therapy: a comprehensive synthesis of emerging cell death paradigms.Oncology reviews · 2026Review
- GATOR1 complex controls cisplatin sensitivity.Cell death & disease · 2025Article
- Cuproplasia and cuproptosis, two sides of the coin.Cancer communications (London, England) · 2025Review
- Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives.Frontiers in pharmacology · 2025Review
- TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Cuproptosis in cancer: biological implications and therapeutic opportunities.Cellular & molecular biology letters · 2024Review
- ATPase Copper Transporting Beta (ATP7B) Is a Novel Target for Improving the Therapeutic Efficacy of Docetaxel by Disulfiram/Copper in Human Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Targeting cuproplasia and cuproptosis in cancer.Nature reviews. Clinical oncology · 2024Review
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning.Frontiers in immunology · 2024Article
- A new glance at autophagolysosomal-dependent or -independent function of transcriptional factor EB in human cancer.Acta pharmacologica Sinica · 2023Review
- The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics.International journal of molecular sciences · 2023Review
- A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach.International journal of molecular sciences · 2023Review
- Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases.Frontiers in pharmacology · 2023Review
- A zinc metabolism-related gene signature for predicting prognosis and characteristics of breast cancer.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
ATP7B is a hepato-specific Golgi-located ATPase, which plays a key role in the regulation of copper (Cu) homeostasis and signaling. In response to elevated Cu levels, ATP7B traffics from the Golgi to endo-lysosomal structures, where it sequesters excess copper and further promotes its excretion to the bile at the apical surface of hepatocytes. In addition to liver, high ATP7B expression has been reported in tumors with elevated resistance to platinum (Pt)-based chemotherapy. Chemoresistance to Pt drugs represents the current major obstacle for the treatment of large cohorts of cancer patients. Although the mechanisms underlying Pt-tolerance are still ambiguous, accumulating evidence suggests that lysosomal sequestration of Pt drugs by ion transporters (including ATP7B) might significantly contribute to drug resistance development. In this context, signaling mechanisms regulating the expression of transporters such as ATP7B are of great importance. Considering this notion, we investigated whether ATP7B expression in Pt-resistant cells might be driven by transcription factor EB (TFEB), a master regulator of lysosomal gene transcription. Using resistant ovarian cancer IGROV-CP20 cells, we found that TFEB directly binds to the predicted coordinated lysosomal expression and regulation (CLEAR) sites in the proximal promoter and first intron region of ATP7B upon Pt exposure. This binding accelerates transcription of luciferase reporters containing ATP7B CLEAR regions, while suppression of TFEB inhibits ATP7B expression and stimulates cisplatin toxicity in resistant cells. Thus, these data have uncovered a Pt-dependent transcriptional mechanism that contributes to cancer chemoresistance and might be further explored for therapeutic purposes.
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