نتائج البحث - "Vousden, Karen, H"

1

دورية أكاديمية

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

المؤلفون: Caswell, Deborah R, Gui, Philippe, Mayekar, Manasi K, Law, Emily K, Pich, Oriol, Bailey, Chris, Boumelha, Jesse, Kerr, D Lucas, Blakely, Collin M, Manabe, Tadashi, Martinez-Ruiz, Carlos, Bakker, Bjorn, De Dios Palomino Villcas, Juan, I. Vokes, Natalie, Dietzen, Michelle, Angelova, Mihaela, Gini, Beatrice, Tamaki, Whitney, Allegakoen, Paul, Wu, Wei, Humpton, Timothy J, Hill, William, Tomaschko, Mona, Lu, Wei-Ting, Haderk, Franziska, Al Bakir, Maise, Nagano, Ai, Gimeno-Valiente, Francisco, de Carné Trécesson, Sophie, Vendramin, Roberto, Barbè, Vittorio, Mugabo, Miriam, Weeden, Clare E, Rowan, Andrew, McCoach, Caroline E, Almeida, Bruna, Green, Mary, Gomez, Carlos, Nanjo, Shigeki, Barbosa, Dora, Moore, Chris, Przewrocka, Joanna, Black, James RM, Grönroos, Eva, Suarez-Bonnet, Alejandro, Priestnall, Simon L, Zverev, Caroline, Lighterness, Scott, Cormack, James, Olivas, Victor, Cech, Lauren, Andrews, Trisha, Rule, Brandon, Jiao, Yuwei, Zhang, Xinzhu, Ashford, Paul, Durfee, Cameron, Venkatesan, Subramanian, Temiz, Nuri Alpay, Tan, Lisa, Larson, Lindsay K, Argyris, Prokopios P, Brown, William L, Yu, Elizabeth A, Rotow, Julia K, Guha, Udayan, Roper, Nitin, Yu, Johnny, Vogel, Rachel I, Thomas, Nicholas J, Marra, Antonio, Selenica, Pier, Yu, Helena, Bakhoum, Samuel F, Chew, Su Kit, Reis-Filho, Jorge S, Jamal-Hanjani, Mariam, Vousden, Karen H, McGranahan, Nicholas, Van Allen, Eliezer M, Kanu, Nnennaya, Harris, Reuben S, Downward, Julian, Bivona, Trever G, Swanton, Charles

المصدر: Nature Genetics. 56(1)

الوصف: In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7vb2s1fwTest

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2

دورية أكاديمية

Cycling back to folate metabolism in cancer

المؤلفون: Younghwan, Lee, Vousden, Karen H., Hennequart, Marc

المصدر: Younghwan , L , Vousden , K H & Hennequart , M 2024 , ' Cycling back to folate metabolism in cancer ' , Nature Cancer . https://doi.org/10.1038/s43018-024-00739-8Test

العلاقة: https://researchportal.unamur.be/en/publications/eb15b202-5d82-4101-94ff-4a5198efa9feTest

الإتاحة: https://doi.org/10.1038/s43018-024-00739-8Test
https://researchportal.unamur.be/en/publications/eb15b202-5d82-4101-94ff-4a5198efa9feTest

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3

دورية أكاديمية

Phenotypic profiling of solute carriers characterizes serine transport in cancer

المؤلفون: Papalazarou, Vasileios, Newman, Alice Claire, Huerta-Uribe, Alejandro, Legrave, Nathalie M., Falcone, Mattia, Zhang, Tong, McGarry, Lynn, Athineos, Dimitris, Shanks, Emma, Blyth, Karen, Vousden, Karen H., Maddocks, Oliver David Kenneth

الوصف: Raw data files associated with the manuscript of the paper - https://www.nature.com/articles/s42255-023-00936-2Test

وصف الملف: Spreadsheet; Text

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4

دورية أكاديمية

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

المؤلفون: Caswell, Deborah R., Gui, Philippe, Mayekar, Manasi K., Law, Emily K., Pich, Oriol, Bailey, Chris, Boumelha, Jesse, Kerr, D. Lucas, Blakely, Collin M., Manabe, Tadashi, Martinez-Ruiz, Carlos, Bakker, Bjorn, De Dios Palomino Villcas, Juan, I. Vokes, Natalie, Dietzen, Michelle, Angelova, Mihaela, Gini, Beatrice, Tamaki, Whitney, Allegakoen, Paul, Wu, Wei, Humpton, Timothy J., Hill, William, Tomaschko, Mona, Lu, Wei Ting, Haderk, Franziska, Al Bakir, Maise, Nagano, Ai, Gimeno-Valiente, Francisco, de Carné Trécesson, Sophie, Vendramin, Roberto, Barbè, Vittorio, Mugabo, Miriam, Weeden, Clare E., Rowan, Andrew, McCoach, Caroline E., Almeida, Bruna, Green, Mary, Gomez, Carlos, Nanjo, Shigeki, Barbosa, Dora, Moore, Chris, Przewrocka, Joanna, Black, James R.M., Grönroos, Eva, Suarez-Bonnet, Alejandro, Priestnall, Simon L., Zverev, Caroline, Lighterness, Scott, Cormack, James, Olivas, Victor, Cech, Lauren, Andrews, Trisha, Rule, Brandon, Jiao, Yuwei, Zhang, Xinzhu, Ashford, Paul, Durfee, Cameron, Venkatesan, Subramanian, Temiz, Nuri Alpay, Tan, Lisa, Larson, Lindsay K., Argyris, Prokopios P., Brown, William L., Yu, Elizabeth A., Rotow, Julia K., Guha, Udayan, Roper, Nitin, Yu, Johnny, Vogel, Rachel I., Thomas, Nicholas J., Marra, Antonio, Selenica, Pier, Yu, Helena, Bakhoum, Samuel F., Chew, Su Kit, Reis-Filho, Jorge S., Jamal-Hanjani, Mariam, Vousden, Karen H., McGranahan, Nicholas, Van Allen, Eliezer M., Kanu, Nnennaya, Harris, Reuben S., Downward, Julian, Bivona, Trever G., Swanton, Charles

المصدر: Caswell , D R , Gui , P , Mayekar , M K , Law , E K , Pich , O , Bailey , C , Boumelha , J , Kerr , D L , Blakely , C M , Manabe , T , Martinez-Ruiz , C , Bakker , B , De Dios Palomino Villcas , J , I. Vokes , N , Dietzen , M , Angelova , M , Gini , B , Tamaki , W , Allegakoen , P , Wu , W , Humpton , T J , Hill , W , Tomaschko ....

مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being, /dk/atira/pure/subjectarea/asjc/1300/1311, name=Genetics

الوصف: In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

وصف الملف: application/pdf

العلاقة: https://researchonline.gcu.ac.uk/en/publications/3ac2b828-a0b7-4092-87f9-41de57e68147Test

الإتاحة: https://doi.org/10.1038/s41588-023-01592-8Test
https://researchonline.gcu.ac.uk/en/publications/3ac2b828-a0b7-4092-87f9-41de57e68147Test
https://researchonline.gcu.ac.uk/ws/files/82378837/82377644.pdfTest

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5

دورية أكاديمية

A celebration of the life of George Vande Woude

المؤلفون: VandeWoude, Sue, Vousden, Karen H.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2021 Dec 01. 118(49), 1-3.

الوصول الحر: https://www.jstor.org/stable/27094108Test

النص الكامل

6

دورية أكاديمية

Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling. ...

المؤلفون: Hobor, Sebastijan, Al Bakir, Maise, Hiley, Crispin T, Skrzypski, Marcin, Frankell, Alexander M, Bakker, Bjorn, Watkins, Thomas BK, Markovets, Aleksandra, Dry, Jonathan R, Brown, Andrew P, van der Aart, Jasper, van den Bos, Hilda, Spierings, Diana, Oukrif, Dahmane, Novelli, Marco, Chakrabarti, Turja, Rabinowitz, Adam H, Hassou, Laila Ait, Litière, Saskia, Kerr, D Lucas, Tan, Lisa, Kelly, Gavin, Moore, David A, Renshaw, Matthew J, Venkatesan, Subramanian, Hill, William, Huebner, Ariana, Martínez-Ruiz, Carlos, Black, James RM, Wu, Wei, Angelova, Mihaela, McGranahan, Nicholas, Downward, Julian, Chmielecki, Juliann, Barrett, Carl, Litchfield, Kevin, Chew, Su Kit, Blakely, Collin M, de Bruin, Elza C, Foijer, Floris, Vousden, Karen H, Bivona, Trever G, consortium, TRACERx, Hynds, Robert E, Kanu, Nnennaya, Zaccaria, Simone, Grönroos, Eva, Swanton, Charles

مصطلحات موضوعية: Tumour Biology, Genetics & Genomics

الوصف: The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an ...

الإتاحة: https://doi.org/10.25418/crick.26038318Test
https://crick.figshare.com/articles/journal_contribution/Mixed_responses_to_targeted_therapy_driven_by_chromosomal_instability_through_p53_dysfunction_and_genome_doubling_/26038318Test

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7

دورية أكاديمية

Cycling back to folate metabolism in cancer. ...

المؤلفون: Lee, Younghwan, Vousden, Karen H, Hennequart, Marc

مصطلحات موضوعية: Tumour Biology, Metabolism

الوصف: Metabolic changes contribute to cancer initiation and progression through effects on cancer cells, the tumor microenvironment and whole-body metabolism. Alterations in serine metabolism and the control of one-carbon cycles have emerged as critical for the development of many tumor types. In this Review, we focus on the mitochondrial folate cycle. We discuss recent evidence that, in addition to supporting nucleotide synthesis, mitochondrial folate metabolism also contributes to metastasis through support of antioxidant defense, mitochondrial protein synthesis and the overflow of excess formate. These observations offer potential therapeutic opportunities, including the modulation of formate metabolism through dietary interventions and the use of circulating folate cycle metabolites as biomarkers for cancer detection. ...

الإتاحة: https://doi.org/10.25418/crick.25921138Test
https://crick.figshare.com/articles/journal_contribution/Cycling_back_to_folate_metabolism_in_cancer_/25921138Test

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8

دورية أكاديمية

Apoptotic cell death in disease—Current understanding of the NCCD 2023

المؤلفون: Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart, A, Abrams, John, M, Adam, Dieter, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad, S, Altucci, Lucia, Amelio, Ivano, Andrews, David, W, Aqeilan, Rami, I, Arama, Eli, Baehrecke, Eric, H, Balachandran, Siddharth, Bano, Daniele, Barlev, Nickolai, A, Bartek, Jiri, Bazan, Nicolas, G, Becker, Christoph, Bernassola, Francesca, Bertrand, Mathieu, J M, Bianchi, Marco, E, Blagosklonny, Mikhail, V, Blander, J. Magarian, Blandino, Giovanni, Blomgren, Klas, Borner, Christoph, Bortner, Carl, D, Bove, Pierluigi, Boya, Patricia, Brenner, Catherine, Broz, Petr, Brunner, Thomas, Damgaard, Rune Busk, Calin, George, A, Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis, Chen, Guo-Qiang, Chen, Quan, Chen, Youhai, H, Cheng, Emily, H, Chipuk, Jerry, E, Cidlowski, John, A, Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Cubillos-Ruiz, Juan, R, Czabotar, Peter, E, D’angiolella, Vincenzo, Daugaard, Mads, Dawson, Ted, M, Dawson, Valina, L, de Maria, Ruggero, de Strooper, Bart, Debatin, Klaus-Michael, Deberardinis, Ralph, J, Degterev, Alexei, del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott, J, Dynlacht, Brian, D, El-Deiry, Wafik, S, Elrod, John, W, Engeland, Kurt, Fimia, Gian Maria, Galassi, Claudia, Ganini, Carlo, Garcia-Saez, Ana, J, Garg, Abhishek, D, Garrido, Carmen, Gavathiotis, Evripidis, Gerlic, Motti, Ghosh, Sourav, Green, Douglas, R, Greene, Lloyd, A, Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J. Marie, Haupt, Ygal, He, Sudan, Heery, David, M, Hengartner, Michael, O, Hetz, Claudio, Hildeman, David, A, Ichijo, Hidenori, Inoue, Satoshi, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp, J, Kanneganti, Thirumala-Devi, Karin, Michael, Kashkar, Hamid, Kaufmann, Thomas, Kelly, Gemma, L, Kepp, Oliver, Kimchi, Adi, Kitsis, Richard, N, Klionsky, Daniel, J, Kluck, Ruth, Krysko, Dmitri, V, Kulms, Dagmar, Kumar, Sharad, Lavandero, Sergio, Lavrik, Inna, N, Lemasters, John, J, Liccardi, Gianmaria, Linkermann, Andreas, Lipton, Stuart, A, Lockshin, Richard, A, López-Otín, Carlos, Luedde, Tom, Macfarlane, Marion, Madeo, Frank, Malorni, Walter, Manic, Gwenola, Mantovani, Roberto, Marchi, Saverio, Marine, Jean-Christophe, Martin, Seamus, J, Martinou, Jean-Claude, Mastroberardino, Pier, G, Medema, Jan Paul, Mehlen, Patrick, Meier, Pascal, Melino, Gerry, Melino, Sonia, Miao, Edward, A, Moll, Ute, M, Muñoz-Pinedo, Cristina, Murphy, Daniel, J, Niklison-Chirou, Maria Victoria, Novelli, Flavia, Núñez, Gabriel, Oberst, Andrew, Ofengeim, Dimitry, Opferman, Joseph, T, Oren, Moshe, Pagano, Michele, Panaretakis, Theocharis, Pasparakis, Manolis, Penninger, Josef, M, Pentimalli, Francesca, Pereira, David, M, Pervaiz, Shazib, Peter, Marcus, E, Pinton, Paolo, Porta, Giovanni, Prehn, Jochen, H M, Puthalakath, Hamsa, Rabinovich, Gabriel, A, Rajalingam, Krishnaraj, Ravichandran, Kodi, S, Rehm, Markus, Ricci, Jean-Ehrland, Rizzuto, Rosario, Robinson, Nirmal, Rodrigues, Cecilia, M P, Rotblat, Barak, Rothlin, Carla, V, Rubinsztein, David, C, Rudel, Thomas, Rufini, Alessandro, Ryan, Kevin, M, Sarosiek, Kristopher, A, Sawa, Akira, Sayan, Emre, Schroder, Kate, Scorrano, Luca, Sesti, Federico, Shao, Feng, Shi, Yufang, Sica, Giuseppe, S, Silke, John, Simon, Hans-Uwe, Sistigu, Antonella, Stephanou, Anastasis, Stockwell, Brent, R, Strapazzon, Flavie, Strasser, Andreas, Sun, Liming, Sun, Erwei, Sun, Qiang, Szabadkai, Gyorgy, Tait, Stephen, W G, Tang, Daolin, Tavernarakis, Nektarios, Troy, Carol, M, Turk, Boris, Urbano, Nicoletta, Vandenabeele, Peter, Vanden Berghe, Tom, Vander Heiden, Matthew, G, Vanderluit, Jacqueline, L, Verkhratsky, Alexei, Villunger, Andreas, von Karstedt, Silvia, Voss, Anne, K, Vousden, Karen, H, Vucic, Domagoj, Vuri, Daniela, Wagner, Erwin, F, Walczak, Henning, Wallach, David, Wang, Ruoning, Wang, Ying, Weber, Achim, Wood, Will, Yamazaki, Takahiro, Yang, Huang-Tian, Zakeri, Zahra, Zawacka-Pankau, Joanna, E, Zhang, Lin, Zhang, Haibing, Zhivotovsky, Boris, Zhou, Wenzhao, Piacentini, Mauro, Kroemer, Guido, Galluzzi, Lorenzo

المساهمون: Institut Gustave Roussy (IGR), Métabolisme, Cancer et Immunité (CRC - UMR_S 1138), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cancer Research and Personalized Medicine - CARPEM Paris (SIRIC CARPEM), Hôpital Européen Georges Pompidou APHP (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer (INCa)-Université Paris Cité (UPCité), ANR-21-ESRE-0028,ONCO-PHENO-SCREEN,Next-generation phenotypic screening for oncological applications(2021)

المصدر: ISSN: 1350-9047.

مصطلحات موضوعية: BAX, BCL2, cancer, death receptors, ischemia, mitochondrial outer membrane permeabilization, stroke, [SDV]Life Sciences [q-bio]

الوصف: International audience

العلاقة: hal-04596448; https://hal.science/hal-04596448Test; https://hal.science/hal-04596448/documentTest; https://hal.science/hal-04596448/file/37100955.pdfTest

الإتاحة: https://doi.org/10.1038/s41418-023-01153-wTest
https://hal.science/hal-04596448Test
https://hal.science/hal-04596448/documentTest
https://hal.science/hal-04596448/file/37100955.pdfTest

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9

دورية أكاديمية

Phenotypic profiling of solute carriers characterizes serine transport in cancer

المؤلفون: Papalazarou, Vasileios, Newman, Alice C., Huerta-Uribe, Alejandro, Legrave, Nathalie M., Falcone, Mattia, Zhang, Tong, McGarry, Lynn, Athineos, Dimitris, Shanks, Emma, Blyth, Karen, Vousden, Karen H., Maddocks, Oliver D. K.

الوصف: Serine is a vital amino acid in tumorigenesis. While cells can perform de novo serine synthesis, most transformed cells rely on serine uptake to meet their increased biosynthetic requirements. Solute carriers (SLCs), a family of transmembrane nutrient transport proteins, are the gatekeepers of amino acid acquisition and exchange in mammalian cells and are emerging as anticancer therapeutic targets; however, the SLCs that mediate serine transport in cancer cells remain unknown. Here we perform an arrayed RNAi screen of SLC-encoding genes while monitoring amino acid consumption and cell proliferation in colorectal cancer cells using metabolomics and high-throughput imaging. We identify SLC6A14 and SLC25A15 as major cytoplasmic and mitochondrial serine transporters, respectively. We also observe that SLC12A4 facilitates serine uptake. Dual targeting of SLC6A14 and either SLC25A15 or SLC12A4 diminishes serine uptake and growth of colorectal cancer cells in vitro and in vivo, particularly in cells with compromised de novo serine biosynthesis. Our results provide insight into the mechanisms that contribute to serine uptake and intracellular handling.

وصف الملف: text

العلاقة: https://eprints.gla.ac.uk/315239/1/315239.pdfTest; Papalazarou, V. et al. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism , 5(12), pp. 2148-2168. (doi:10.1038/s42255-023-00936-2 ) (PMID:38066114) (PMCID:PMC10730406)

الإتاحة: https://doi.org/10.1038/s42255-023-00936-2Test
https://eprints.gla.ac.uk/315239Test/
https://eprints.gla.ac.uk/315239/1/315239.pdfTest

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10

دورية أكاديمية

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

المؤلفون: Caswell, Deborah R, Gui, Philippe, Mayekar, Manasi K, Law, Emily K, Pich, Oriol, Bailey, Chris, Boumelha, Jesse, Kerr, D Lucas, Blakely, Collin M, Manabe, Tadashi, Martinez-Ruiz, Carlos, Bakker, Bjorn, De Dios Palomino Villcas, Juan, I Vokes, Natalie, Dietzen, Michelle, Angelova, Mihaela, Gini, Beatrice, Tamaki, Whitney, Allegakoen, Paul, Wu, Wei, Humpton, Timothy J, Hill, William, Tomaschko, Mona, Lu, Wei-Ting, Haderk, Franziska, Al Bakir, Maise, Nagano, Ai, Gimeno-Valiente, Francisco, de Carné Trécesson, Sophie, Vendramin, Roberto, Barbè, Vittorio, Mugabo, Miriam, Weeden, Clare E, Rowan, Andrew, McCoach, Caroline E, Almeida, Bruna, Green, Mary, Gomez, Carlos, Nanjo, Shigeki, Barbosa, Dora, Moore, Chris, Przewrocka, Joanna, Black, James RM, Grönroos, Eva, Suarez-Bonnet, Alejandro, Priestnall, Simon L, Zverev, Caroline, Lighterness, Scott, Cormack, James, Olivas, Victor, Cech, Lauren, Andrews, Trisha, Rule, Brandon, Jiao, Yuwei, Zhang, Xinzhu, Ashford, Paul, Durfee, Cameron, Venkatesan, Subramanian, Temiz, Nuri Alpay, Tan, Lisa, Larson, Lindsay K, Argyris, Prokopios P, Brown, William L, Yu, Elizabeth A, Rotow, Julia K, Guha, Udayan, Roper, Nitin, Yu, Johnny, Vogel, Rachel I, Thomas, Nicholas J, Marra, Antonio, Selenica, Pier, Yu, Helena, Bakhoum, Samuel F, Chew, Su Kit, Reis-Filho, Jorge S, Jamal-Hanjani, Mariam, Vousden, Karen H, McGranahan, Nicholas, Van Allen, Eliezer M, Kanu, Nnennaya, Harris, Reuben S, Downward, Julian, Bivona, Trever G, Swanton, Charles

المصدر: Nature Genetics (2023) (In press).

الوصف: In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10183369/1/s41588-023-01592-8.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10183369Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10183369/1/s41588-023-01592-8.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10183369Test/

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