title: Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.
abstract: The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF" by Heidorn and colleagues, published in Cell in 2010 (Heidorn et al., 2010). The experiments to be replicated are those reported in Figures 1A, 1B, 3A, 3B, and 4D. Heidorn and colleagues report that paradoxical activation of the RAF-RAS-MEK-ERK pathway by BRAF inhibitors when applied to BRAF(WT) cells is a result of BRAF/CRAF heterodimer formation upon inactivation of BRAF kinase activity, and occurs only in the context of active RAS. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.
authors.affiliation: Shakti BioResearch LLC, Woodbridge, United States.
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhargava
authors.affiliation: Shakti BioResearch LLC, Woodbridge, United States.
authors.forename: Madan
authors.initials: M
authors.lastname: Anant
authors.affiliation: University of California, San Francisco, San Francisco, United States.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Mack
mesh_terms: D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D011485:Protein Binding; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D015689:Oncogene Protein p21(ras)
keywords: B-RAF; K-RAS; cancer biology; human; melanoma; methodology; reproducibility project: cancer biology