ArticleCancer discovery2013
Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 142 papers.
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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.
The trial behind it
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
142 citing papers in PubMed, 225 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Immunogenic Cell Death in Melanoma Induced by Radiotherapy, Photodynamic Therapy, or Non-Thermal Plasma: The Role of Reactive Oxygen and Nitrogen Species.Biomedicines · 2026Review
- Imaging of ROR1 expression in tumors using radiolabeled affibody molecules.European journal of nuclear medicine and molecular imaging · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- The Influence of Dietary and Physical Exercise Habits on Melanoma Risk: A Case-Control Study.Nutrients · 2026Article
- Rapid activation of ARF6 after RAF inhibition augments BRAFOncogene · 2026Article
- Modulating tumor mechanics and vascular barriers to enhance chemotherapy efficacy in pancreatic tumors and melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Towards epigenetically informed and biobank-driven precision immunotherapy in melanoma.Frontiers in immunology · 2026Review
- Article
- Rapid activation of ARF6 after RAF inhibition augments BRAFV600E and promotes therapy resistance.Research square · 2025Article
- Review
- GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation.EMBO reports · 2025Article
- Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression.Nature communications · 2025Article
- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
- Polyoxygenated cembrane-type diterpenes from the Hainan soft coral Lobophytum crassum as a promising source of anticancer agents with ErbB3 and ROR1 inhibitory potential.Acta pharmacologica Sinica · 2025Article
- Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials.Cells · 2024Review
- ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.Cancer discovery · 2024Article
- Article
- Genomic and transcriptomic landscape to decipher the genetic basis of hyperpigmentation in Lanping black-boned sheep (Ovis aries).BMC genomics · 2024Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 5 institutions in 1 country.
Funding
Abstract
unlabelledAn emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive phenotype to a highly invasive, less proliferative one. This switch may hold significant implications not just for metastasis, but also for therapy resistance. We demonstrate that phenotype switching and subsequent resistance can be guided by changes in expression of receptors involved in the noncanonical Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Furthermore, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. Notably, this receptor switch induces a 10-fold decrease in sensitivity to BRAF inhibitors. In patients with melanoma treated with the BRAF inhibitor vemurafenib, Wnt5A expression correlates with clinical response and therapy resistance. These data highlight the fact that mechanisms that guide metastatic progression may be linked to those that mediate therapy resistance. SIGNIFICANCE: These data show for the fi rst time that a single signaling pathway, the Wnt signaling pathway, can effectively guide the phenotypic plasticity of tumor cells, when primed to do so by a hypoxic microenvironment. Importantly, this increased Wnt5A signaling can give rise to a subpopulation of highly invasive cells that are intrinsically less sensitive to novel therapies for melanoma, and targeting the Wnt5A/ROR2 axis could improve the efficacy and duration of response for patients with melanoma on vemurafenib.
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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.