ArticleOncogene2003
RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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.
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
66 citing papers in PubMed, 177 citations in OpenAlex.
- Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.The New England journal of medicine · 2013Trial
- The impact of RET fusions on radioiodine avidity and prognosis in patients with distant metastatic papillary thyroid cancer.Endocrine · 2026Article
- ERK Signaling in Thyroid Cancer: Lineage Suppression, Epigenetic Reprogramming, and Theranostic Reversal.Cancers · 2026Review
- Radioiodine-Refractory Differentiated Thyroid Cancer: Definition, Molecular Mechanisms, and Advances in Precision Therapy.Cancer innovation · 2026Review
- Article
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- HMGA2 Overexpression in Papillary Thyroid Cancer Promotes Thyroid Cell Dedifferentiation and Invasion, and These Effects Are Counteracted by Suramin.International journal of molecular sciences · 2025Article
- Selpercatinib combination with the mitochondria-targeted antioxidant MitoQ effectively suppresses RET-mutant thyroid cancer.NPJ precision oncology · 2024Article
- Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.American journal of cancer research · 2024Review
- MicroRNA 452 regulates SHC1 expression in human colorectal cancer and colitis.Genes & genomics · 2023Article
- Pathogenesis of cancers derived from thyroid follicular cells.Nature reviews. Cancer · 2023Review
- The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients.European journal of nuclear medicine and molecular imaging · 2023Article
- Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Construction of a Signature Model to Predict the Radioactive Iodine Response of Papillary Thyroid Cancer.Frontiers in endocrinology · 2022Article
- Osteopontin Expression in Thyroid Cancer: Deciphering EMT-Related Molecular Mechanisms.Biomedicines · 2021Review
- Co-inhibition of SMAD and MAPK signaling enhances 124I uptake in BRAF-mutant thyroid cancers.Endocrine-related cancer · 2021Article
- Molecular pathogenesis of pediatric thyroid carcinoma.Journal of radiation research · 2021Review
- Review
- Update on Fundamental Mechanisms of Thyroid Cancer.Frontiers in endocrinology · 2020Review
- Nevirapine Increases Sodium/Iodide Symporter-Mediated Radioiodide Uptake by Activation of TSHR/cAMP/CREB/PAX8 Signaling Pathway in Dedifferentiated Thyroid Cancer.Frontiers in oncology · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Constitutive activation of the RET proto-oncogene in papillary thyroid carcinomas results from rearrangements linking the promoter(s) and N-terminal domains of unrelated genes to the C-terminus of RET tyrosine kinase (RET/PTC). RET/PTC expression has been demonstrated to inhibit transcription of thyroid-specific genes. To study the signal transduction pathways responsible for this, we generated PCCL3 thyroid cells with doxycycline-inducible expression of RET/PTC3, RET/PTC3(Y541F), or PTC2/PDZ. Acute expression of RET/PTC(Y541F) appropriately interacted with Shc, an intermediate in the activation of the Ras pathway, but failed to activate PLCgamma. By contrast, PTC2/PDZ failed to bind Shc, but interacted normally with PLCgamma. Acute expression of RET/PTC3 or RET/PTC3(Y541F), but not PTC2/PDZ, inhibited TSH-induced Tg and NIS expression, suggesting that activation of Shc-Ras, but not PLCgamma, is required for RET/PTC-induced dedifferentiation. Accordingly, acute expression of H-Ras(V12) or of a constitutively active MEK1 also blocked TSH-induced expression of Tg and NIS. Moreover, MEK inhibitors restored Tg and NIS levels. In conclusion, activation of the Ras/Raf/MEK/MAPK pathway through Shc mediates RET/PTC-induced thyroid cell dedifferentiation. This suggests that inhibition of this pathway may promote redifferentiation in poorly differentiated thyroid carcinomas with constitutive activation of either Ras or RET/PTC.
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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.