ArticleAutophagy2016
Metastatic risk and resistance to BRAF inhibitors in melanoma defined by selective allelic loss of ATG5.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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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
25 citing papers in PubMed, 35 citations in OpenAlex.
- The role of Atg5 gene in tumorigenesis under autophagy deficiency conditions.The Kaohsiung journal of medical sciences · 2024Article
- CCDC50 promotes tumor growth through regulation of lysosome homeostasis.EMBO reports · 2023Article
- Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective.Cell death discovery · 2023Review
- Autophagy Paradox: Strategizing Treatment Modality in Melanoma.Current treatment options in oncology · 2023Review
- Article
- The multifaceted role of autophagy in cancer.The EMBO journal · 2022Review
- Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy.Signal transduction and targeted therapy · 2022Review
- Review
- The Pathologic and Genetic Characteristics of Extranodal NK/T-Cell Lymphoma.Life (Basel, Switzerland) · 2022Review
- Autophagy in tumour immunity and therapy.Nature reviews. Cancer · 2021Review
- Non-Apoptotic Cell Death Signaling Pathways in Melanoma.International journal of molecular sciences · 2020Review
- BRAF in malignant melanoma progression and metastasis: potentials and challenges.American journal of cancer research · 2020Review
- Susceptibility and Resistance Mechanisms During Photodynamic Therapy of Melanoma.Frontiers in oncology · 2020Review
- Melanoma in a patient with previously unrecognized Birt-Hogg-Dubé syndrome.JAAD case reports · 2019Article
- Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma.Cell death and differentiation · 2019Article
- A cancer associated somatic mutation in LC3B attenuates its binding to E1-like ATG7 protein and subsequent lipidation.Autophagy · 2019Article
- MITF has a central role in regulating starvation-induced autophagy in melanoma.Scientific reports · 2019Article
- The Complex Role of Autophagy in Melanoma Evolution: New Perspectives From Mouse Models.Frontiers in oncology · 2019Review
- Prostate Cancer Energetics and Biosynthesis.Advances in experimental medicine and biology · 2019Review
- Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Melanoma is a paradigm of aggressive tumors with a complex and heterogeneous genetic background. Still, melanoma cells frequently retain developmental traits that trace back to lineage specification programs. In particular, lysosome-associated vesicular trafficking is emerging as a melanoma-enriched lineage dependency. However, the contribution of other lysosomal functions such as autophagy to melanoma progression is unclear, particularly in the context of metastasis and resistance to targeted therapy. Here we mined a broad spectrum of cancers for a meta-analysis of mRNA expression, copy number variation and prognostic value of 13 core autophagy genes. This strategy identified heterozygous loss of ATG5 at chromosome band 6q21 as a distinctive feature of advanced melanomas. Importantly, partial ATG5 loss predicted poor overall patient survival in a manner not shared by other autophagy factors and not recapitulated in other tumor types. This prognostic relevance of ATG5 copy number was not evident for other 6q21 neighboring genes. Melanocyte-specific mouse models confirmed that heterozygous (but not homozygous) deletion of Atg5 enhanced melanoma metastasis and compromised the response to targeted therapy (exemplified by dabrafenib, a BRAF inhibitor in clinical use). Collectively, our results support ATG5 as a therapeutically relevant dose-dependent rheostat of melanoma progression. Moreover, these data have important translational implications in drug design, as partial blockade of autophagy genes may worsen (instead of counteracting) the malignant behavior of metastatic melanomas.
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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.