ArticleThe Journal of clinical endocrinology and metabolism2014
Switch in signaling control of mTORC1 activity after oncoprotein expression in thyroid cancer cell lines.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 23 citations in OpenAlex.
- Incidence ofThe Journal of international medical research · 2019Trial
- Trial
- Article
- Development of a Risk Predictive Model for Evaluating Immune Infiltration Status in Invasive Thyroid Carcinoma.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Current understanding of nonsurgical interventions for refractory differentiated thyroid cancer: a systematic review.Future science OA · 2021Review
- Thyroid Cancer and Circadian Clock Disruption.Cancers · 2020Review
- Hormonal Regulation of Autophagy in Thyroid PCCL3 Cells and the Thyroids of Male Mice.Journal of the Endocrine Society · 2020Article
- lncRNA SNHG3 acts as a novel Tumor Suppressor and regulates Tumor Proliferation and Metastasis via AKT/mTOR/ERK pathway in Papillary Thyroid Carcinoma.Journal of Cancer · 2020Article
- PKA Activates AMPK Through LKB1 Signaling in Follicular Thyroid Cancer.Frontiers in endocrinology · 2019Article
- The Emerging Role of Insulin Receptor Isoforms in Thyroid Cancer: Clinical Implications and New Perspectives.International journal of molecular sciences · 2018Review
- The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer.Oncogenesis · 2018Article
- Novel targeted therapies and immunotherapy for advanced thyroid cancers.Molecular cancer · 2018Review
- Sustained activation of the AKT/mTOR and MAP kinase pathways mediate resistance to the Src inhibitor, dasatinib, in thyroid cancer.Oncotarget · 2017Article
- Coupling of LETM1 up-regulation with oxidative phosphorylation and platelet-derived growth factor receptor signaling via YAP1 transactivation.Oncotarget · 2016Article
- Selective use of sorafenib in the treatment of thyroid cancer.Drug design, development and therapy · 2016Review
- A novel dual AMPK activator/mTOR inhibitor inhibits thyroid cancer cell growth.The Journal of clinical endocrinology and metabolism · 2015Article
- Autophagy in thyroid cancer: present knowledge and future perspectives.Frontiers in endocrinology · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
contextThyroid growth is regulated by TSH and requires mammalian target of rapamycin (mTOR). Thyroid cancers frequently exhibit mutations in MAPK and/or phosphoinositol-3-kinase-related kinase effectors.
objectiveThe objective of the study was to explore the contribution of RET/PTC, RAS, and BRAF to mTOR regulation and response to mTOR inhibitors.
methodsPCCL3 cells conditionally expressing RET/PTC3, HRAS(G12V), or BRAF(V600E) and human thyroid cancer cells harboring mutations of these genes were used to test pathways controlling mTOR and its requirement for growth.
resultsTSH/cAMP-induced growth of PCCL3 cells requires mTOR, which is stimulated via protein kinase A in a MAPK kinase (MEK)- and AKT-independent manner. Expression of RET/PTC3, HRAS(G12V), or BRAF(V600E) in PCCL3 cells induces mTOR but does not entirely abrogate the cAMP-mediated control of its activity. Acute oncoprotein-induced mTOR activity is regulated by MEK and AKT, albeit to differing degrees. By contrast, mTOR was not activated by TSH/cAMP in human thyroid cancer cells. Tumor genotype did not predict the effects of rapamycin or the mTOR kinase inhibitor AZD8055 on growth, with the exception of a PTEN-null cell line. Selective blockade of MEK did not influence mTOR activity of BRAF or RAS mutant cells. Combined MEK and mTOR kinase inhibition was synergistic on growth of BRAF- and RAS-mutant thyroid cancer cells in vitro and in vivo.
conclusionThyroid cancer cells lose TSH/cAMP dependency of mTOR signaling and cell growth. mTOR activity is not decreased by the MEK or AKT inhibitors in the RAS or BRAF human thyroid cancer cell lines. This may account for the augmented effects of combining the mTOR inhibitors with selective antagonists of these oncogenic drivers.
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