ArticleOncotarget2015
SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
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- JNK1 inhibitors target distal B cell receptor signaling and overcome BTK-inhibitor resistance in CLL.The Journal of experimental medicine · 2025Article
- Characterization of EpCAM in thyroid cancer biology by three-dimensional spheroids in vitro model.Cancer cell international · 2024Article
- Testosterone promotes the migration, invasion and EMT process of papillary thyroid carcinoma by up-regulating Tnnt1.Journal of endocrinological investigation · 2024Article
- Role of ROCK signaling in virus replication.Virus research · 2023Review
- FAM83B is involved in thyroid cancer cell differentiation and migration.Scientific reports · 2022Article
- Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response.Cell reports · 2022Article
- Stress-activated kinases as therapeutic targets in pancreatic cancer.World journal of gastroenterology · 2021Review
- JNK signaling as a target for anticancer therapy.Pharmacological reports : PR · 2021Review
- Selective inhibitors for JNK signalling: a potential targeted therapy in cancer.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Carnosine Impedes PDGF-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro and Sprout Outgrowth Ex Vivo.Nutrients · 2020Article
- Potential synergistic effects of sorafenib and CP-31398 for treating anaplastic thyroid cancer with p53 mutations.Oncology letters · 2020Article
- Regulation of RhoB Gene Expression during Tumorigenesis and Aging Process and Its Potential Applications in These Processes.Cancers · 2019Review
- A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform.BMC cancer · 2019Article
- Forskolin exerts anticancer roles in non-Hodgkin's lymphomas via regulating Axin/β-catenin signaling pathway.Cancer management and research · 2019Article
- Activation of CXCL5-CXCR2 axis promotes proliferation and accelerates G1 to S phase transition of papillary thyroid carcinoma cells and activates JNK and p38 pathways.Cancer biology & therapy · 2019Article
- Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1.Scientific reports · 2018Article
- Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells.Cell death & disease · 2018Article
- JNK, p38, ERK, and SGK1 Inhibitors in Cancer.Cancers · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thyroid cancer is the most common endocrine malignancy with increasing incidence worldwide.The majority of thyroid cancer cases are well differentiated with favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies because of their invasiveness, metastatization and refractoriness even to the most recently developed therapies.In this study we show for the first time a significant hyperactivation of ROCK/HDAC6 pathway in thyroid cancer tissues, and its negative correlation with p53 DNA binding ability.We demonstrate that a small compound, SP600125 (SP), is able to induce cell death selectively in undifferentiated thyroid cancer cell lines by specifically acting on the pathogenic pathways of cancer development. In detail, SP acts on the ROCK/HDAC6 pathway involved in dedifferentiation and invasiveness of undifferentiated human cancers, by restoring its physiological activity level. As main consequence, cancer cell migration is inhibited and, at the same time, cell death is induced through the mitotic catastrophe. Moreover, SP exerts a preferential action on the mutant p53 by increasing its DNA binding ability. In TP53-mutant cells that survive mitotic catastrophe this process results in p21 induction and eventually lead to premature senescence. In conclusion, SP has been proved to be able to simultaneously block cell replication and migration, the two main processes involved in cancer development and dissemination, making it an ideal candidate for developing new drugs against anaplastic thyroid cancer.
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