scholarly journals Registered report: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Mitch Phelps ◽  
Chris Coss ◽  
Hongyan Wang ◽  
Matthew Cook ◽  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Biology ◽  
Target Genes ◽  
Regulatory Mechanism ◽  
Scientific Research ◽  
Open Science ◽  
Competitive Binding ◽  
High Profile ◽  
Competing Endogenous Rnas

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 (<xref ref-type="bibr" rid="bib8">Errington et al., 2014</xref>). This Registered Report describes the proposed replication plan of key experiments from “Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous 'mRNAs' by Tay and colleagues, published in Cell in 2011 (<xref ref-type="bibr" rid="bib23">Tay et al., 2011</xref>). The experiments to be replicated are those reported in Figures 3C, 3D, 3G, 3H, 5A and 5B, and in Supplemental Figures 3A and B. Tay and colleagues proposed a new regulatory mechanism based on competing endogenous RNAs (ceRNAs), which regulate target genes by competitive binding of shared microRNAs. They test their model by identifying and confirming ceRNAs that target PTEN. In Figure 3A and B, they report that perturbing expression of putative PTEN ceRNAs affects expression of PTEN. This effect is dependent on functional microRNA machinery (Figure 3G and H), and affects the pathway downstream of PTEN itself (Figures 5A and B). 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.

scholarly journals Registered report: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Brad Evans ◽  
Erin Griner ◽  
Keyword(s):  
Cancer Cell ◽  
Histone Methylation ◽  
Cancer Biology ◽  
Scientific Research ◽  
Competitive Inhibitor ◽  
Open Science ◽  
High Profile ◽  
Mutant Idh1 ◽  
Mutant Forms

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 (<xref ref-type="bibr" rid="bib3">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases’ by Xu and colleagues, published in Cancer Cell in 2011 (<xref ref-type="bibr" rid="bib15">Xu et al., 2011</xref>). The key experiments being replicated include Supplemental Figure 3I, which demonstrates that transfection with mutant forms of IDH1 increases levels of 2-hydroxyglutarate (2-HG), Figures 3A and 8A, which demonstrate changes in histone methylation after treatment with 2-HG, and Figures 3D and 7B, which show that mutant IDH1 can effect the same changes as treatment with excess 2-HG. 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.

scholarly journals Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ajay Bhargava ◽  
Madan Anant ◽  
Hildegard Mack ◽  
Keyword(s):  
Tumor Progression ◽  
Cancer Biology ◽  
Kinase Activity ◽  
Scientific Research ◽  
Open Science ◽  
Erk Pathway ◽  
Braf Inhibitors ◽  
Oncogenic Ras ◽  
High Profile

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 (<xref ref-type="bibr" rid="bib4">Errington et al., 2014</xref>). 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 (<xref ref-type="bibr" rid="bib9">Heidorn et al., 2010</xref>). 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 BRAFWT 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.

scholarly journals Registered report: Transcriptional amplification in tumor cells with elevated c-Myc

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
David Blum ◽  
Haiping Hao ◽  
Michael McCarthy ◽  
Keyword(s):  
Gene Expression ◽  
Tumor Cells ◽  
Cancer Biology ◽  
Cell Model ◽  
Scientific Research ◽  
Digital Gene Expression ◽  
Open Science ◽  
Large Set ◽  
Mrna Levels ◽  
Transcriptional Amplification

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Transcriptional amplification in tumor cells with elevated c-Myc’ by <xref ref-type="bibr" rid="bib5">Lin et al. (2012)</xref>, published in Cell in 2012. The experiments that will be replicated are those reported in Figures 3E and 3F. In these experiments, elevated levels of c-Myc in the P493-6 cell model of Burkitt's lymphoma results in an increase of the total level of RNA using UV/VIS spectrophotometry (Figure 3E; <xref ref-type="bibr" rid="bib5">Lin et al., 2012</xref>) and on the mRNA levels/cell for a large set of genes using digital gene expression technology (Figure 3F; <xref ref-type="bibr" rid="bib5">Lin et al., 2012</xref>). 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 in eLife.

scholarly journals Registered report: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Israr Khan ◽  
John Kerwin ◽  
Kate Owen ◽  
Erin Griner ◽  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cancer Biology ◽  
Open Science ◽  
Tumor Cell Proliferation ◽  
Independent Function ◽  
Pten Protein ◽  
Protein Levels ◽  
High Profile ◽  
Tumour Biology

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 (<xref ref-type="bibr" rid="bib9">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘A coding-independent function of gene and pseudogene mRNAs regulates tumour biology’ by <xref ref-type="bibr" rid="bib26">Poliseno et al. (2010)</xref>, published in Nature in 2010. The key experiments to be replicated are reported in Figures 1D, 2F-H, and 4A. In these experiments, Poliseno and colleagues report microRNAs miR-19b and miR-20a transcriptionally suppress both PTEN and PTENP1 in prostate cancer cells (Figure 1D; <xref ref-type="bibr" rid="bib26">Poliseno et al., 2010</xref>). Decreased expression of PTEN and/or PTENP1 resulted in downregulated PTEN protein levels (Figure 2H), downregulation of both mRNAs (Figure 2G), and increased tumor cell proliferation (Figure 2F; <xref ref-type="bibr" rid="bib26">Poliseno et al., 2010</xref>). Furthermore, overexpression of the PTEN 3′ UTR enhanced PTENP1 mRNA abundance limiting tumor cell proliferation, providing additional evidence for the co-regulation of PTEN and PTENP1 (Figure 4A; <xref ref-type="bibr" rid="bib26">Poliseno et al., 2010</xref>). The Reproducibility Project: Cancer Biology is collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published in eLife.

scholarly journals Registered report: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
David Blum ◽  
Samuel LaBarge ◽  
Keyword(s):  
Cell Lines ◽  
Cancer Biology ◽  
Stromal Cell ◽  
Drug Sensitivity ◽  
Scientific Research ◽  
Open Science ◽  
Innate Resistance

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from ‘Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion’ by Straussman and colleagues, published in Nature in 2012 (<xref ref-type="bibr" rid="bib10">Straussman et al., 2012</xref>). The key experiments being replicated in this study are from Figure 2A, C, and D (and Supplemental Figure 11) and Figure 4C (and Supplemental Figure 19) (<xref ref-type="bibr" rid="bib10">Straussman et al., 2012</xref>). Figure 2 demonstrates resistance to drug sensitivity conferred by co-culture with some stromal cell lines and identifies the secreted factor responsible as HGF. In Figure 4, Straussman and colleagues show that blocking the HGF receptor MET abrogates HGF’s rescue of drug sensitivity. 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.

scholarly journals Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Oliver Fiehn ◽  
Megan Reed Showalter ◽  
Christine E Schaner-Tooley ◽  
Keyword(s):  
Enzyme Activity ◽  
Myeloid Leukemia ◽  
Cancer Biology ◽  
Open Science ◽  
Wild Type ◽  
High Profile ◽  
Isocitrate Dehydrogenase 2 ◽  
The Common ◽  
Idh1 And Idh2 Mutations ◽  
Acute Myeloid

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 (<xref ref-type="bibr" rid="bib3">Errington et al., 2014</xref>). This Registered Report describes the proposed replication plan of key experiments from “The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate” by Ward and colleagues, published in Cancer Cell in 2010 (<xref ref-type="bibr" rid="bib16">Ward et al., 2010</xref>). The experiments that will be replicated are those reported in Figures 2, 3 and 5. Ward and colleagues demonstrate the mutations in isocitrate dehydrogenase 2 (IDH2), commonly found in acute myeloid leukemia (AML), abrogate the enzyme’s wild-type activity and confer to the mutant neomorphic activity that produces the oncometabolite 2-hydroxyglutarate (2-HG) (Figures 2 and 3). They then show that elevated levels of 2-HG are correlated with mutations in IDH1 and IDH2 in AML patient samples (Figure 5). 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.

scholarly journals Registered report: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Steven Fiering ◽  
Lay-Hong Ang ◽  
Judith Lacoste ◽  
Tim D Smith ◽  
Erin Griner ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Cancer Biology ◽  
Xenograft Model ◽  
Open Science ◽  
Original Publication ◽  
Metastasis Formation ◽  
Invasion And Metastasis ◽  
Caveolin 1 ◽  
High Profile ◽  
Subcutaneous Xenograft

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replicating selected results 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 Altimetric scores (<xref ref-type="bibr" rid="bib5a">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ by Goetz and colleagues, published in Cell in 2011 (<xref ref-type="bibr" rid="bib8">Goetz et al., 2011</xref>). The key experiments being replicated are those reported in Figures 7C (a-d), Supplemental Figure S2A, and Supplemental Figure S7C (a-c) (<xref ref-type="bibr" rid="bib8">Goetz et al., 2011</xref>). In these experiments, which are a subset of all the experiments reported in the original publication, Goetz and colleagues show in a subcutaneous xenograft model that stromal caveolin-1 remodels the intratumoral microenvironment, which is correlated with increased metastasis formation. 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 in eLife.

scholarly journals Registered report: Interactions between cancer stem cells and their niche govern metastatic colonization

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Francesca Incardona ◽  
M Mehdi Doroudchi ◽  
Nawfal Ismail ◽  
Alberto Carreno ◽  
Erin Griner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Open Science ◽  
Metastatic Niche ◽  
Pulmonary Fibroblasts ◽  
Metastatic Colonization ◽  
High Profile ◽  
Tumor Growth And Metastasis

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by replicating selected results from a substantial number of high-profile papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Interactions between cancer stem cells and their niche govern metastatic colonization’ by Malanchi and colleagues, published in Nature in 2012 (<xref ref-type="bibr" rid="bib10">Malanchi et al., 2012</xref>). The key experiments that will be replicated are those reported in Figures 2H, 3A, 3B, and S13. In these experiments, Malanchi and colleagues analyze messenger RNA levels of periostin (POSTN) in pulmonary fibroblasts, endothelial cells, and immune cells isolated from mice with micrometastases to determine which cell type is producing POSTN in the metastatic niche (Figure 2H; <xref ref-type="bibr" rid="bib10">Malanchi et al., 2012</xref>). Additionally, they examine MMTV-PyMT control or POSTN null mice to test the effect of POSTN on primary tumor growth and metastasis (Figures 3A, 3B, and S13; <xref ref-type="bibr" rid="bib10">Malanchi et al., 2012</xref>). 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 in eLife.

scholarly journals Registered report: IDH mutation impairs histone demethylation and results in a block to cell differentiation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Adam D Richarson ◽  
David A Scott ◽  
Olga Zagnitko ◽  
Pedro Aza-Blanc ◽  
Chih-Cheng Chang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Histone Methylation ◽  
Cancer Biology ◽  
Scientific Research ◽  
Histone Demethylase ◽  
Idh Mutation ◽  
Histone Demethylation ◽  
High Profile ◽  
Mutant Forms

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 “IDH mutation impairs histone demethylation and results in a block to cell differentiation” by Lu and colleagues, published in Nature in 2012 (Lu et al., 2012). The experiments that will be replicated are those reported in Figures 1B, 2A, 2B, 2D and 4D. Lu and colleagues demonstrated that expression of mutant forms of IDH1 or IDH2 caused global increases in histone methylation and increased levels of 2 hydroxyglutarate (Figure 1B). This was correlated with a block in differentiation (Figures 2A, B and D). This effect appeared to be mediated by the histone demethylase KDM4C (Figure 4D). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Scienceand Science Exchange, and the results of the replications will be published by eLife.

scholarly journals Registered report: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Irawati Kandela ◽  
James Chou ◽  
Kartoa Chow ◽  
Keyword(s):  
Cell Death ◽  
Body Weight ◽  
Cancer Biology ◽  
Scientific Research ◽  
Open Science ◽  
Cancer Drugs ◽  
Tumor Weight

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs’ by Sugahara and colleagues, published in Science in 2010 (<xref ref-type="bibr" rid="bib10">Sugahara et al., 2010</xref>). The key experiments being replicated include Figure 2 and Supplemental Figure 9A. In Figure 2, Sugahara and colleagues presented data on the tumor penetrance of doxorubicin (DOX) when co-administered with the peptide iRGD, as well as the effect of co-treatment of DOX and iRGD on tumor weight and cell death. In Supplemental Figure 9A, they tracked body weight of mice treated with DOX and iRGD to provide evidence that iRGD does not increase known DOX toxicity. 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.

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