ArticleNature medicine2011
A MEK-independent role for CRAF in mitosis and tumor progression.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- In-cell single-molecule FRET measurement of cytosolic RAF proteins to investigate the structural states and kinetics among them.Frontiers in molecular biosciences · 2025Article
- Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage.Nature communications · 2024Article
- SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling.Life science alliance · 2024Article
- The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.Nature reviews. Cancer · 2024Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- RAF1 contributes to cell proliferation and STAT3 activation in colorectal cancer independently of microsatellite and KRAS status.Oncogene · 2023Article
- Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na).Pharmaceutics · 2023Review
- Hyper-active RAS/MAPK introduces cancer-specific mitotic vulnerabilities.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis.Nature communications · 2022Article
- Autocrine GMCSF Signaling Contributes to Growth of HER2Cancer research · 2021Article
- Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells.Nature communications · 2021Article
- RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis.Nature communications · 2021Article
- YWHAE-NUTM2 oncoprotein regulates proliferation and cyclin D1 via RAF/MAPK and Hippo pathways.Oncogenesis · 2021Article
- Review
- Precision Chemoradiotherapy for HER2 Tumors Using Antibody Conjugates of an Auristatin Derivative with Reduced Cell Permeability.Molecular cancer therapeutics · 2020Article
- Nuclear localized Raf1 isoform alters DNA-dependent protein kinase activity and the DNA damage response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Loss of USP28-mediated BRAF degradation drives resistance to RAF cancer therapies.The Journal of experimental medicine · 2018Article
- Article
- The effects of trastuzumab on HER2-mediated cell signaling in CHO cells expressing human HER2.BMC cancer · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
RAF kinases regulate cell proliferation and survival and can be dysregulated in tumors. The role of RAF in cell proliferation has been linked to its ability to activate mitogen-activated protein kinase kinase 1 (MEK) and mitogen-activated protein kinase 1 (ERK). Here we identify a MEK-independent role for RAF in tumor growth. Specifically, in mitotic cells, CRAF becomes phosphorylated on Ser338 and localizes to the mitotic spindle of proliferating tumor cells in vitro as well as in murine tumor models and in biopsies from individuals with cancer. Treatment of tumors with allosteric inhibitors, but not ATP-competitive RAF inhibitors, prevents CRAF phosphorylation on Ser338 and localization to the mitotic spindle and causes cell-cycle arrest at prometaphase. Furthermore, we identify phospho-Ser338 CRAF as a potential biomarker for tumor progression and a surrogate marker for allosteric RAF blockade. Mechanistically, CRAF, but not BRAF, associates with Aurora kinase A (Aurora-A) and Polo-like kinase 1 (Plk1) at the centrosomes and spindle poles during G2/M. Indeed, allosteric or genetic inhibition of phospho-Ser338 CRAF impairs Plk1 activation and accumulation at the kinetochores, causing prometaphase arrest, whereas a phospho-mimetic Ser338D CRAF mutant potentiates Plk1 activation, mitosis and tumor progression in mice. These findings show a previously undefined role for RAF in tumor progression beyond the RAF-MEK-ERK paradigm, opening new avenues for targeting RAF in cancer.
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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.