ArticleNeoplasia (New York, N.Y.)2009
RET/PTC1-driven neoplastic transformation and proinvasive phenotype of human thyrocytes involve Met induction and beta-catenin nuclear translocation.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Cabozantinib in progressive medullary thyroid cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- General Assessment of Indole Derivatives and Wnt Pathway as Potential Key Factors Against Various Diseases, with Particular Emphasis on Thyroid Tumors.International journal of molecular sciences · 2026Review
- Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer.MedComm · 2024Article
- Recombinant Human TSH Fails to Induce the Proliferation and Migration of Papillary Thyroid Carcinoma Cell Lines.Cancers · 2024Article
- Tumor-associated macrophages: role in cancer development and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2019Review
- Coding Molecular Determinants of Thyroid Cancer Development and Progression.Endocrinology and metabolism clinics of North America · 2019Review
- Cigarette smoke enhances oncogene addiction to c-MET and desensitizes EGFR-expressing non-small cell lung cancer to EGFR TKIs.Molecular oncology · 2018Article
- Review
- Apatinib-treated advanced medullary thyroid carcinoma: a case report.OncoTargets and therapy · 2018Article
- Upregulation of RSPO2-GPR48/LGR4 signaling in papillary thyroid carcinoma contributes to tumor progression.Oncotarget · 2017Article
- Medullary Thyroid Cancer: Clinical Characteristics and New Insights into Therapeutic Strategies Targeting Tyrosine Kinases.Molecular diagnosis & therapy · 2017Review
- Activated E2F activity induces cell death in papillary thyroid carcinoma K1 cells with enhanced Wnt signaling.PloS one · 2017Article
- β-catenin signaling is required for RAS-driven thyroid cancer through PI3K activation.Oncotarget · 2016Article
- Review
- Population Pharmacokinetic Model of Cabozantinib in Patients with Medullary Thyroid Carcinoma and Its Application to an Exposure-Response Analysis.Clinical pharmacokinetics · 2016Article
- Article
- Autophagy in thyroid cancer: present knowledge and future perspectives.Frontiers in endocrinology · 2015Review
- Selective inhibition of RET mediated cell proliferation in vitro by the kinase inhibitor SPP86.BMC cancer · 2014Article
- A phase I study of cabozantinib (XL184) in patients with differentiated thyroid cancer.Thyroid : official journal of the American Thyroid Association · 2014Article
- Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC). We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, beta-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and beta-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F) devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of beta-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated beta-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes beta-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs.
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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.