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3. Metabolism‐focused CRISPR screen unveils mitochondrial pyruvate carrier 1 as a critical driver for PARP inhibitor resistance in lung cancer

Author

Furusawa, Takashi, primary, Cavero, Renzo, additional, Liu, Yue, additional, Li, Haojian, additional, Xu, Xia, additional, Andresson, Thorkell, additional, Reinhold, William, additional, White, Olivia, additional, Boufraqech, Myriem, additional, Meyer, Thomas J., additional, Hartmann, Oliver, additional, Diefenbacher, Markus E., additional, Pommier, Yves, additional, and Weyemi, Urbain, additional

Published
2024
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4. Metabolism-focused CRISPR screen unveils Mitochondrial Pyruvate Carrier 1 as a critical driver for PARP inhibitor resistance in lung cancer

Author

Furusawa, Takashi, primary, Cavero, Renzo, additional, Liu, Yue, additional, Li, Haojian, additional, Xu, Xia, additional, Andresson, Thorkell, additional, Reinhold, William, additional, White, Olivia, additional, Boufraqech, Myriem, additional, Meyer, Thomas J, additional, Hartmann, Oliver, additional, Diefenbacher, Markus E, additional, Pommier, Yves, additional, and Weyemi, Urbain, additional

Published
2023
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7. Supplementary information from A Combinatorial Strategy for Targeting BRAFV600E-Mutant Cancers with BRAFV600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)

Author

Ghosh, Chandrayee, primary, Kumar, Suresh, primary, Kushchayeva, Yevgeniya, primary, Gaskins, Kelli, primary, Boufraqech, Myriem, primary, Wei, Darmood, primary, Gara, Sudheer Kumar, primary, Zhang, Lisa, primary, Zhang, Ya-qin, primary, Shen, Min, primary, Mukherjee, Sanjit, primary, and Kebebew, Electron, primary

Published
2023
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8. Appendix 1 from Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo

Author

Thakur, Shilpa, primary, Daley, Brianna, primary, Gaskins, Kelli, primary, Vasko, Vasyl V., primary, Boufraqech, Myriem, primary, Patel, Dhaval, primary, Sourbier, Carole, primary, Reece, Jeff, primary, Cheng, Sheue-Yann, primary, Kebebew, Electron, primary, Agarwal, Sunita, primary, and Klubo-Gwiezdzinska, Joanna, primary

Published
2023
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9. Supplementary file from Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo

Author

Thakur, Shilpa, primary, Daley, Brianna, primary, Gaskins, Kelli, primary, Vasko, Vasyl V., primary, Boufraqech, Myriem, primary, Patel, Dhaval, primary, Sourbier, Carole, primary, Reece, Jeff, primary, Cheng, Sheue-Yann, primary, Kebebew, Electron, primary, Agarwal, Sunita, primary, and Klubo-Gwiezdzinska, Joanna, primary

Published
2023
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11. APPENDIX 3 from Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo

Author

Thakur, Shilpa, primary, Daley, Brianna, primary, Gaskins, Kelli, primary, Vasko, Vasyl V., primary, Boufraqech, Myriem, primary, Patel, Dhaval, primary, Sourbier, Carole, primary, Reece, Jeff, primary, Cheng, Sheue-Yann, primary, Kebebew, Electron, primary, Agarwal, Sunita, primary, and Klubo-Gwiezdzinska, Joanna, primary

Published
2023
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12. Data from A Combinatorial Strategy for Targeting BRAFV600E-Mutant Cancers with BRAFV600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)

Author

Ghosh, Chandrayee, primary, Kumar, Suresh, primary, Kushchayeva, Yevgeniya, primary, Gaskins, Kelli, primary, Boufraqech, Myriem, primary, Wei, Darmood, primary, Gara, Sudheer Kumar, primary, Zhang, Lisa, primary, Zhang, Ya-qin, primary, Shen, Min, primary, Mukherjee, Sanjit, primary, and Kebebew, Electron, primary

Published
2023
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14. APPENDIX 2 from Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo

Author

Thakur, Shilpa, primary, Daley, Brianna, primary, Gaskins, Kelli, primary, Vasko, Vasyl V., primary, Boufraqech, Myriem, primary, Patel, Dhaval, primary, Sourbier, Carole, primary, Reece, Jeff, primary, Cheng, Sheue-Yann, primary, Kebebew, Electron, primary, Agarwal, Sunita, primary, and Klubo-Gwiezdzinska, Joanna, primary

Published
2023
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15. Supplemental Figure 1 from miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

Author

Boufraqech, Myriem, primary, Nilubol, Naris, primary, Zhang, Lisa, primary, Gara, Sudheer Kumar, primary, Sadowski, Samira M., primary, Mehta, Amit, primary, He, Mei, primary, Davis, Sean, primary, Dreiling, Jennifer, primary, Copland, John A., primary, Smallridge, Robert C., primary, Quezado, Martha M., primary, and Kebebew, Electron, primary

Published
2023
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17. Supplemental Figure 3 from miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

Author

Boufraqech, Myriem, primary, Nilubol, Naris, primary, Zhang, Lisa, primary, Gara, Sudheer Kumar, primary, Sadowski, Samira M., primary, Mehta, Amit, primary, He, Mei, primary, Davis, Sean, primary, Dreiling, Jennifer, primary, Copland, John A., primary, Smallridge, Robert C., primary, Quezado, Martha M., primary, and Kebebew, Electron, primary

Published
2023
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19. Supplemental Figure 2 from miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

Author

Boufraqech, Myriem, primary, Nilubol, Naris, primary, Zhang, Lisa, primary, Gara, Sudheer Kumar, primary, Sadowski, Samira M., primary, Mehta, Amit, primary, He, Mei, primary, Davis, Sean, primary, Dreiling, Jennifer, primary, Copland, John A., primary, Smallridge, Robert C., primary, Quezado, Martha M., primary, and Kebebew, Electron, primary

Published
2023
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20. CRISPR metabolic screen identifies ATM and KEAP1 as targetable genetic vulnerabilities in solid tumors

Author

Li, Haojian, primary, Liu, Yue, additional, Xiao, Yunjie, additional, Wilson, Crystal N., additional, Bai, Hui Jen, additional, Jones, Maxwell D., additional, Wang, Shihchun, additional, DeVore, Jennie E., additional, Maier, Esther Y., additional, Durant, Stephen T., additional, Boufraqech, Myriem, additional, and Weyemi, Urbain, additional

Published
2023
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24. Preclinical Assessment of Synergistic Efficacy of MELK and CDKs inhibitors in Adrenocortical Cancer

Author

LAHA, DIPRANJAN, primary, Grant, Robert, additional, Mishra, Prachi, additional, Boufraqech, Myriem, additional, Shen, Min, additional, Zhang, Ya-Qin, additional, Hall, Matthew D., additional, Quezado, Martha, additional, De Melo, Michelly Sampaio, additional, Rivero, Jaydira Del, additional, Zeiger, Martha, additional, and Nilubol, Naris, additional

Published
2022
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25. Additional file 3 of Preclinical assessment of synergistic efficacy of MELK and CDK inhibitors in adrenocortical cancer

Author

Laha, Dipranjan, Grant, Robert R.C., Mishra, Prachi, Boufraqech, Myriem, Shen, Min, Zhang, Ya-Qin, Hall, Matthew D., Quezado, Martha, De Melo, Michelly Sampaio, Del Rivero, Jaydira, Zeiger, Martha, and Nilubol, Naris

Abstract

Additionalfile 3: Supplementary Table 1. List of 30 selected drugs for combination drug screening in ACC cell lines. Supplementary Table 2. Correlations between mRNA expression of CDKs and cyclin molecules with MKI67 in human ACC from the TCGA cohort Supplementary Table 3. Correlations between mRNA expression of CDKs and cyclin molecules with MELK in human ACC samples from the TCGA cohort. Supplementary Table 4. OTS167 and RGB-286638 combination shows synergistic activity in ACC cells. The combination index (CI) was calculated using the Chou–Talalay method. The CI is determined by the following range: CI < 1, synergistic; CI = 1, additive; CI > 1, antagonistic. Supplementary Table 5. Correlations between mRNA expression of MELK and β-catenin regulatory molecules in human ACC samples from the TCGA cohort Supplementary Table 6. Correlations between mRNA expression of CDKs and cyclin molecules with STMN1 in human ACC samples from the TCGA cohort Supplementary Table 7. List of Antibodies.

Published
2022
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27. Additional file 2 of Preclinical assessment of synergistic efficacy of MELK and CDK inhibitors in adrenocortical cancer

Author

Laha, Dipranjan, Grant, Robert R.C., Mishra, Prachi, Boufraqech, Myriem, Shen, Min, Zhang, Ya-Qin, Hall, Matthew D., Quezado, Martha, De Melo, Michelly Sampaio, Del Rivero, Jaydira, Zeiger, Martha, and Nilubol, Naris

Abstract

Additional file 2: Supplementary Figure 1. CDKs and cyclin molecules are overexpressed in ACC: A mRNA expression of CDK1 and CDK2 (NC vs. ACC) from the publicly available data set GSE90713 (NC = 5, ACC = 57) (p < 0.05). B mRNA expression of CCNA2, C mRNA expression of CCNB1, D mRNA expression of CCNB2, and E mRNA expression of CCNE2, from the GSE33371, GSE12638, and GSE90713 data sets. Supplementary Figure 2. Cyclin molecule overexpression correlates with poor prognosis in ACC: A Kaplan-Meier survival curve representing the OS in the TCGA ACC cohort with low and high expression of CCNA2, CCNB1, and CCNB2. B Kaplan-Meier survival curve representing the overall DFS in the TCGA ACC cohort with low and high expression of CCNA2, CCNB1, and CCNB2. C, D Differential mRNA expression of CCNA2, CCNB1, and CCNB2 by over all stages and T stage in the TCGA ACC cohort. All data were analyzed by two-tailed unpaired Student’s t-test or one-way ANOVA. Supplementary Figure 3. Cyclin E2 is associated with poor prognosis of patients with ACC: A, B Kaplan-Meier survival curve representing the overall and DFS in the TCGA ACC cohort with high and low CCNE2expression. High CCNE2 expression (red); low CCNE2 expression (blue) (*p < 0.01). C CCNE2 expression by over all stage and T stage in the TCGA ACC cohort (*p < 0.05). Supplementary Figure 4. Cleaved Caspase 3 expression in SW13 and NCI-H295R cells treated with OTS167, RGB-286638, and OTS167 and RGB-286638 combined for 24 and 48 hours respectively. Cells were stain with cleaved caspase 3 conjugated with Alexa Fluor® 555 Conjugate (Red). Actin filaments and nuclei were labeled with Alexa Fluor 488 phalloidin (green) and DAPI respectively. The images were taken under confocal microscopsy (Zeiss) at 63X. Supplementary Figure 5. FOXM1 is overexpressed in advanced tumor stage and correlated with poor prognosis of ACC patient: A mRNA expression of FOXM1 in the publicly available data sets GSE33371 (NC vs. ACC, ACA vs. ACC) (p < 0.001) and GSE12368 (NC vs. ACC, ACA vs. ACC) (p < 0.05). B, C Kaplan-Meier survival curve and DFS curve of patients with ACC, stratified by FOXM1 expression level. D, E, F Differential expression of FOXM1 mRNA by stage, tumor grade status, and lymph node status. Supplementary Figure 6. MELK inhibition affects β-catenin pathway in ACC cells: A SW13 and NCI-H295R cells were treated with OTS167. Expression of MELK in SW13 and NCI-H295R cells treated with OTS167 for 24–72 hours. B Expression of β-catenin, FOXM1, GSK-3β, and Axin 2 in siMELK and siNegative transfected cells.

Published
2022
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28. CRISPR metabolic screen identifies ATM and KEAP1 as targetable genetic vulnerabilities in solid tumors.

Author

Haojian Li, Yue Liu, Yunjie Xiao, Wilson, Crystal N., Hui Jen Bai, Jones, Maxwell D., Shihchun Wang, DeVore, Jennie E., Maier, Esther Y., Durant, Stephen T., Boufraqech, Myriem, and Weyemi, Urbain

Subjects
DNA repair, AUTOMATED teller machines, CRISPRS, MEDICAL screening, GENETIC counseling, GLUTAMATE transporters
Abstract

Cancer treatments targeting DNA repair deficiencies often encounter drug resistance, possibly due to alternative metabolic pathways that counteract the most damaging effects. To identify such alternative pathways, we screened for metabolic pathways exhibiting synthetic lethality with inhibition of the DNA damage response kinase Ataxia-telangiectasia-mutated (ATM) using a metabolism-centered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 library. Our data revealed Kelch-like ECH-associated protein 1 (KEAP1) as a key factor involved in desensitizing cancer cells to ATM inhibition both in vitro and in vivo. Cells depleted of KEAP1 exhibited an aberrant overexpression of the cystine transporter SLC7A11, robustly accumulated cystine inducing disulfide stress, and became hypersensitive to ATM inhibition. These hallmarks were reversed in a reducing cellular environment indicating that disulfide stress was a crucial factor. In The Cancer Genome Atlas (TCGA) pan-cancer datasets, we found that ATM levels negatively correlated with KEAP1 levels across multiple solid malignancies. Together, our results unveil ATM and KEAP1 as new targetable vulnerabilities in solid tumors. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Role of H2O2inRET/PTC1Chromosomal Rearrangement Produced by Ionizing Radiation in Human Thyroid Cells.

Author

Ameziane-El-Hassani, Rabii, primary, Boufraqech, Myriem, additional, Lagente-Chevallier, Odile, additional, Weyemi, Urbain, additional, Talbot, Monique, additional, Metivier, Didier, additional, Courtin, Françoise, additional, Bidart, Jean-Michel, additional, El Mzibri, Mohammed, additional, Schlumberger, Martin, additional, and Dupuy, Corinne, additional

Published
2010
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39. A Combinatorial Strategy for Targeting BRAFV600E-Mutant Cancers with BRAFV600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)

Author

Ghosh, Chandrayee, primary, Kumar, Suresh, additional, Kushchayeva, Yevgeniya, additional, Gaskins, Kelli, additional, Boufraqech, Myriem, additional, Wei, Darmood, additional, Gara, Sudheer Kumar, additional, Zhang, Lisa, additional, Zhang, Ya-qin, additional, Shen, Min, additional, Mukherjee, Sanjit, additional, and Kebebew, Electron, additional

Published
2020
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44. Lysyl Oxidase Is a Key Player in BRAF/MAPK Pathway-Driven Thyroid Cancer Aggressiveness

Author

Boufraqech, Myriem, primary, Patel, Dhaval, additional, Nilubol, Naris, additional, Powers, Astin, additional, King, Timothy, additional, Shell, Jasmine, additional, Lack, Justin, additional, Zhang, Lisa, additional, Gara, Sudheer Kumar, additional, Gunda, Viswanath, additional, Klubo-Gwiezdzinska, Joanna, additional, Kumar, Suresh, additional, Fagin, James, additional, Knauf, Jeffrey, additional, Parangi, Sareh, additional, Venzon, David, additional, Quezado, Martha, additional, and Kebebew, Electron, additional

Published
2019
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46. Transcriptional alterations in hereditary and sporadic nonfunctioning pancreatic neuroendocrine tumors according to genotype

Author

Keutgen, Xavier M., Kumar, Suresh, Gara, Sudheer, Boufraqech, Myriem, Agarwal, Sunita, Hruban, Ralph H., Nilubol, Naris, Quezado, Martha, Finney, Richard, Cam, Maggie, and Kebebew, Electron

Subjects
Pancreatic Neoplasms, Receptor, Platelet-Derived Growth Factor beta, Gene Ontology, Genotype, Transcription, Genetic, Von Hippel-Lindau Tumor Suppressor Protein, Cluster Analysis, Humans, Cyclin-Dependent Kinase 6, Article
Abstract

Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed by real-time polymerase chain reaction analysis and immunohistochemistry. Gene expression profiles were analyzed by tumor genotype, and pathway analysis was curated.Consensus clustering of mRNA expression revealed separate clustering of NICs, VHL-associated NFPanNETs, and MEN1-associated NFPanNETs; whereas some sporadic tumors clustered with MEN1. Four of 5 MEN1-like sporadic PanNET subtypes had loss of heterozygosity at the MEN1 gene locus. Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and cilium/microtubule development in sporadic NFPanNETs. Among many genes, platelet-derived growth factor receptor β (PDGFRB), lymphoid enhancer-binding factor-1 (Lef-1), cyclin-dependent kinase 4 (CDK4), and CDK6 were upregulated in VHL or MEN1 NFPanNETs, providing potential subtype-specific treatment targets.Distinct mRNA expression patterns were identified in sporadic-associated, VHL-associated, and MEN1-associated NFPanNETs. The current results uncover new pathways involved in NFPanNETs that are subtype-specific and provide potential new diagnostic or therapeutic targets based on tumor subtype. Cancer 2018;124:636-47. © 2017 American Cancer Society.

Published
2017

48. Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo

Author

Thakur, Shilpa, primary, Daley, Brianna, additional, Gaskins, Kelli, additional, Vasko, Vasyl V., additional, Boufraqech, Myriem, additional, Patel, Dhaval, additional, Sourbier, Carole, additional, Reece, Jeff, additional, Cheng, Sheue-Yann, additional, Kebebew, Electron, additional, Agarwal, Sunita, additional, and Klubo-Gwiezdzinska, Joanna, additional

Published
2018
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49. 68-Gallium DOTATATE scanning in symptomatic patients with negative anatomic imaging but suspected neuroendocrine tumor

Author

Shell, Jasmine, primary, Keutgen, Xavier M, additional, Millo, Corina, additional, Nilubol, Naris, additional, Patel, Dhaval, additional, Sadowski, Samira, additional, Boufraqech, Myriem, additional, Yang, Lily, additional, Merkel, Roxanne, additional, Atallah, Christine, additional, Herscovitch, Peter, additional, and Kebebew, Electron, additional

Published
2018
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