ArticleCell cycle (Georgetown, Tex.)2012
E2F1 confers anticancer drug resistance by targeting ABC transporter family members and Bcl-2 via the p73/DNp73-miR-205 circuitry.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma.Physiological genomics · 2013Pooled it
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- MiRNAs: main players of cancer drug resistance target ABC transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The E2F family: a ray of dawn in cardiomyopathy.Molecular and cellular biochemistry · 2025Review
- DTL promotes the growth and migration of melanoma cells through the ERK/E2F1/BUB1 axis.Scientific reports · 2024Article
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- microRNA-205 in prostate cancer: Overview to clinical translation.Biochimica et biophysica acta. Reviews on cancer · 2022Review
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- Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis.International journal of molecular sciences · 2022Article
- Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells.World journal of surgical oncology · 2022Article
- Identification of ABCA5 among ATP-Binding Cassette Transporter Family as a New Biomarker for Colorectal Cancer.Journal of oncology · 2022Article
- The Role of MicroRNAs in Cancer Biology and Therapy from a Systems Biology Perspective.Advances in experimental medicine and biology · 2022Review
- Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells.Molecular biology · 2022Article
- Mechanisms of Functional Pleiotropy of p73 in Cancer and Beyond.Frontiers in cell and developmental biology · 2021Review
- Transcriptional E2F1/2/3/6 as potential prognostic biomarkers in cutaneous melanoma.American journal of translational research · 2021Article
- Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms.Cell death & disease · 2020Review
- Upregulation of miR-34c after silencing E2F transcription factor 1 inhibits paclitaxel combined with cisplatin resistance in gastric cancer cells.World journal of gastroenterology · 2020Article
- SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors.Science advances · 2019Article
- The broken cycle: E2F dysfunction in cancer.Nature reviews. Cancer · 2019Review
- Overexpression of long non-coding RNA NORAD promotes invasion and migration in malignant melanoma via regulating the MIR-205-EGLN2 pathway.Cancer medicine · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to anti-neoplastic agents is the major cause of therapy failure, leading to disease recurrence and metastasis. E2F1 is a strong inducer of apoptosis in response to DNA damage through its capacity to activate p53/p73 death pathways. Recent evidence, however, showed that E2F1, which is aberrantly expressed in advanced malignant melanomas together with antagonistic p73 family members, drives cancer progression. Investigating mechanisms responsible for dysregulated E2F1 losing its apoptotic function, we searched for genomic signatures in primary and late clinical tumor stages to allow the prediction of downstream effectors associated with apoptosis resistance and survival of aggressive melanoma cells. We identified miR-205 as specific target of p73 and found that upon genotoxic stress, its expression is sufficiently abrogated by endogenous DNp73. Significantly, metastatic cells can be rescued from drug resistance by selective knockdown of DNp73 or overexpression of miR-205 in p73-depleted cells, leading to increased apoptosis and the reduction of tumor growth in vivo. Our data delineate an autoregulatory circuit, involving high levels of E2F1 and DNp73 to downregulate miR-205, which, in turn, controls E2F1 accumulation. Finally, drug resistance associated to this genetic signature is mediated by removing the inhibitory effect of miR-205 on the expression of Bcl-2 and the ATP-binding cassette transporters A2 (ABCA2) and A5 (ABCA5) related to multi-drug resistance and malignant progression. These results define the E2F1-p73/DNp73-miR-205 axis as a crucial mechanism for chemoresistance and, thus, as a target for metastasis prevention.
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