ArticleMolecular and cellular biology2003
The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 120 citations in OpenAlex.
- Phase II trial of sorafenib in metastatic thyroid cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Targeting cancer-associated fibroblast-driven LIF/LIFR axis improves the therapeutic efficacy of gemcitabine and nab-paclitaxel in pancreatic cancer.NPJ precision oncology · 2025Article
- Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments.Journal of personalized medicine · 2023Review
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- Leukemia Inhibitory Factor: An Important Cytokine in Pathologies and Cancer.Biomolecules · 2022Review
- Analogs of the Heat Shock Protein 70 Inhibitor MKT-077 Suppress Medullary Thyroid Carcinoma Cells.International journal of molecular sciences · 2022Article
- eIF5A-Independent Role of DHPS in p21International journal of molecular sciences · 2021Article
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- The emerging role of leukemia inhibitory factor in cancer and therapy.Pharmacology & therapeutics · 2021Review
- An engineered ligand trap inhibits leukemia inhibitory factor as pancreatic cancer treatment strategy.Communications biology · 2021Article
- Specific and Aspecific Molecular Checkpoints as Potential Targets for Dismantling Tumor Hierarchy and Preventing Relapse and Metastasis Through Shielded Cytolytic Treatments.Frontiers in cell and developmental biology · 2021Article
- Article
- Similarities Between Embryo Development and Cancer Process Suggest New Strategies for Research and Therapy of Tumors: A New Point of View.Frontiers in cell and developmental biology · 2019Article
- A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses.Cellular signalling · 2018Article
- Vandetanib and cabozantinib potentiate mitochondria-targeted agents to suppress medullary thyroid carcinoma cells.Cancer biology & therapy · 2017Article
- Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation.Scientific reports · 2016Article
- KRASG12 mutant induces the release of the WSTF/NRG3 complex, and contributes to an oncogenic paracrine signaling pathway.Oncotarget · 2016Article
- Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo.Endocrinology and metabolism (Seoul, Korea) · 2015Article
- High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma.Oncotarget · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sustained activation of the Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) pathway can lead to cell cycle arrest in many cell types. We have found, with human medullary thyroid cancer (MTC) cells, that activated Ras or c-Raf-1 can induce growth arrest by producing and secreting an autocrine-paracrine factor. This protein was purified from cell culture medium conditioned by Raf-activated MTC cells and was identified by mass spectrometry as leukemia inhibitory factor (LIF). LIF expression upon Raf activation and subsequent activation of JAK-STAT3 was also observed in small cell lung carcinoma cells, suggesting that this autocrine-paracrine signaling may be a common response to Ras/Raf activation. LIF was sufficient to induce growth arrest and differentiation of MTC cells. This effect was mediated through the gp130/JAK/STAT3 pathway, since anti-gp130 blocking antibody or dominant-negative STAT3 blocked the effects of LIF. Thus, LIF expression provides a novel mechanism allowing Ras/Raf signaling to activate the JAK-STAT3 pathway. In addition to this cell-extrinsic growth inhibitory pathway, we find that the Ras/Raf/MEK/ERK pathway induces an intracellular growth inhibitory signal, independent of the LIF/JAK/STAT3 pathway. Therefore, activation of the Ras/Raf/MEK/ERK pathway can lead to growth arrest and differentiation via at least two different signaling pathways. This use of multiple pathways may be important for "fail-safe" induction and maintenance of cell cycle arrest.
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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.