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3. Truncated FGFR2 is a clinically actionable oncogene in multiple cancers

Author

Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M., Rolfs, Frank, Lutz, Catrin, Lee, Jessica K., Klarenbeek, Sjoerd, Silverman, Ian M., Annunziato, Stefano, Chan, Chang S., Piersma, Sander R., Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R., Riedlinger, Gregory M., Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H., Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R., Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K., Ross, Jeffrey S., van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M., Burn, Timothy C., Jimenez, Connie R., Ganesan, Shridar, Wessels, Lodewyk F. A., and Jonkers, Jos

Published
2022
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4. MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling

Author

Zimmerli, Dario, Brambillasca, Chiara S., Talens, Francien, Bhin, Jinhyuk, Linstra, Renske, Romanens, Lou, Bhattacharya, Arkajyoti, Joosten, Stacey E. P., Da Silva, Ana Moises, Padrao, Nuno, Wellenstein, Max D., Kersten, Kelly, de Boo, Mart, Roorda, Maurits, Henneman, Linda, de Bruijn, Roebi, Annunziato, Stefano, van der Burg, Eline, Drenth, Anne Paulien, Lutz, Catrin, Endres, Theresa, van de Ven, Marieke, Eilers, Martin, Wessels, Lodewyk, de Visser, Karin E., Zwart, Wilbert, Fehrmann, Rudolf S. N., van Vugt, Marcel A. T. M., and Jonkers, Jos

Published
2022
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5. Publisher Correction: Truncated FGFR2 is a clinically actionable oncogene in multiple cancers

Author

Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M., Rolfs, Frank, Lutz, Catrin, Lee, Jessica K., Klarenbeek, Sjoerd, Silverman, Ian M., Annunziato, Stefano, Chan, Chang S., Piersma, Sander R., Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R., Riedlinger, Gregory M., Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H., Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R., Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K., Ross, Jeffrey S., van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M., Burn, Timothy C., Jimenez, Connie R., Ganesan, Shridar, Wessels, Lodewyk F. A., and Jonkers, Jos

Published
2022
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8. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis

Author

Wellenstein, Max D., Coffelt, Seth B., Duits, Danique E. M., van Miltenburg, Martine H., Slagter, Maarten, de Rink, Iris, Henneman, Linda, Kas, Sjors M., Prekovic, Stefan, Hau, Cheei-Sing, Vrijland, Kim, Drenth, Anne Paulien, de Korte-Grimmerink, Renske, Schut, Eva, van der Heijden, Ingrid, Zwart, Wilbert, Wessels, Lodewyk F. A., Schumacher, Ton N., Jonkers, Jos, and de Visser, Karin E.

Published
2019
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9. In situ CRISPR‐Cas9 base editing for the development of genetically engineered mouse models of breast cancer

Author

Annunziato, Stefano, Lutz, Catrin, Henneman, Linda, Bhin, Jinhyuk, Wong, Kim, Siteur, Bjørn, van Gerwen, Bas, de Korte‐Grimmerink, Renske, Zafra, Maria Paz, Schatoff, Emma M, Drenth, Anne Paulien, van der Burg, Eline, Eijkman, Timo, Mukherjee, Siddhartha, Boroviak, Katharina, Wessels, Lodewyk FA, van de Ven, Marieke, Huijbers, Ivo J, Adams, David J, Dow, Lukas E, and Jonkers, Jos

Published
2020
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10. Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer

Author

Annunziato, Stefano, de Ruiter, Julian R., Henneman, Linda, Brambillasca, Chiara S., Lutz, Catrin, Vaillant, François, Ferrante, Federica, Drenth, Anne Paulien, van der Burg, Eline, Siteur, Bjørn, van Gerwen, Bas, de Bruijn, Roebi, van Miltenburg, Martine H., Huijbers, Ivo J., van de Ven, Marieke, Visvader, Jane E., Lindeman, Geoffrey J., Wessels, Lodewyk F. A., and Jonkers, Jos

Published
2019
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11. Data from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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12. Supplementary Figure 3 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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13. Supplementary Figure 1 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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14. Supplementary Figure 4 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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15. Supplementary Figure Legends 1-5 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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16. Supplementary Table 2 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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17. Supplementary Table 1 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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18. Supplementary Figure 5 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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19. Supplementary Figure 2 from TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary

Published
2023
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22. Publisher Correction:Truncated FGFR2 is a clinically actionable oncogene in multiple cancers (Nature, (2022), 608, 7923, (609-617), 10.1038/s41586-022-05066-5)

Author

Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M., Rolfs, Frank, Lutz, Catrin, Lee, Jessica K., Klarenbeek, Sjoerd, Silverman, Ian M., Annunziato, Stefano, Chan, Chang S., Piersma, Sander R., Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R., Riedlinger, Gregory M., Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H., Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R., Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K., Ross, Jeffrey S., van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M., Burn, Timothy C., Jimenez, Connie R., Ganesan, Shridar, Wessels, Lodewyk F. A., Jonkers, Jos, Medical oncology laboratory, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and Amsterdam Neuroscience - Neurodegeneration

Abstract

This paper was originally published under a standard Springer Nature license (

Published
2022
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23. Posttranslational modification of microtubules by the MATCAP detyrosinase

Author

Landskron, Lisa, Bak, Jitske, Adamopoulos, Athanassios, Kaplani, Konstantina, Moraiti, Maria, van den Hengel, Lisa G., Song, Ji Ying, Bleijerveld, Onno B., Nieuwenhuis, Joppe, Heidebrecht, Tatjana, Henneman, Linda, Moutin, Marie Jo, Barisic, Marin, Taraviras, Stavros, Perrakis, Anastassis, Brummelkamp, Thijn R., Landskron, Lisa, Bak, Jitske, Adamopoulos, Athanassios, Kaplani, Konstantina, Moraiti, Maria, van den Hengel, Lisa G., Song, Ji Ying, Bleijerveld, Onno B., Nieuwenhuis, Joppe, Heidebrecht, Tatjana, Henneman, Linda, Moutin, Marie Jo, Barisic, Marin, Taraviras, Stavros, Perrakis, Anastassis, and Brummelkamp, Thijn R.

Abstract

The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of a-tubulin and is implicated in cognitive, cardiac, and mitotic defects. The vasohibin–small vasohibin-binding protein (SVBP) complex underlies much, but not all, detyrosination. We used haploid genetic screens to identify an unannotated protein, microtubule associated tyrosine carboxypeptidase (MATCAP), as a remaining detyrosinating enzyme. X-ray crystallography and cryo–electron microscopy structures established MATCAP’s cleaving mechanism, substrate specificity, and microtubule recognition. Paradoxically, whereas abrogation of tyrosine religation is lethal in mice, codeletion of MATCAP and SVBP is not. Although viable, defective detyrosination caused microcephaly, associated with proliferative defects during neurogenesis, and abnormal behavior. Thus, MATCAP is a missing component of the detyrosination-tyrosination cycle, revealing the importance of this modification in brain formation.

Published
2022

24. MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling

Author

Hubrecht Institute with UMC, Zimmerli, Dario, Brambillasca, Chiara S., Talens, Francien, Bhin, Jinhyuk, Linstra, Renske, Romanens, Lou, Bhattacharya, Arkajyoti, Joosten, Stacey E.P., Da Silva, Ana Moises, Padrao, Nuno, Wellenstein, Max D., Kersten, Kelly, de Boo, Mart, Roorda, Maurits, Henneman, Linda, de Bruijn, Roebi, Annunziato, Stefano, van der Burg, Eline, Drenth, Anne Paulien, Lutz, Catrin, Endres, Theresa, van de Ven, Marieke, Eilers, Martin, Wessels, Lodewyk, de Visser, Karin E., Zwart, Wilbert, Fehrmann, Rudolf S.N., van Vugt, Marcel A.T.M., Jonkers, Jos, Hubrecht Institute with UMC, Zimmerli, Dario, Brambillasca, Chiara S., Talens, Francien, Bhin, Jinhyuk, Linstra, Renske, Romanens, Lou, Bhattacharya, Arkajyoti, Joosten, Stacey E.P., Da Silva, Ana Moises, Padrao, Nuno, Wellenstein, Max D., Kersten, Kelly, de Boo, Mart, Roorda, Maurits, Henneman, Linda, de Bruijn, Roebi, Annunziato, Stefano, van der Burg, Eline, Drenth, Anne Paulien, Lutz, Catrin, Endres, Theresa, van de Ven, Marieke, Eilers, Martin, Wessels, Lodewyk, de Visser, Karin E., Zwart, Wilbert, Fehrmann, Rudolf S.N., van Vugt, Marcel A.T.M., and Jonkers, Jos

Published
2022

25. Publisher Correction: Truncated FGFR2 is a clinically actionable oncogene in multiple cancers

Author

CMM Groep De Keizer, Cancer, CMM Groep Cuppen, Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M, Rolfs, Frank, Lutz, Catrin, Lee, Jessica K, Klarenbeek, Sjoerd, Silverman, Ian M, Annunziato, Stefano, Chan, Chang S, Piersma, Sander R, Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R, Riedlinger, Gregory M, Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H, Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R, Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K, Ross, Jeffrey S, van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M, Burn, Timothy C, Jimenez, Connie R, Ganesan, Shridar, Wessels, Lodewyk F A, Jonkers, Jos, CMM Groep De Keizer, Cancer, CMM Groep Cuppen, Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M, Rolfs, Frank, Lutz, Catrin, Lee, Jessica K, Klarenbeek, Sjoerd, Silverman, Ian M, Annunziato, Stefano, Chan, Chang S, Piersma, Sander R, Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R, Riedlinger, Gregory M, Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H, Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R, Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K, Ross, Jeffrey S, van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M, Burn, Timothy C, Jimenez, Connie R, Ganesan, Shridar, Wessels, Lodewyk F A, and Jonkers, Jos

Published
2022

27. Posttranslational modification of microtubules by the MATCAP detyrosinase

Author

Landskron, Lisa, primary, Bak, Jitske, additional, Adamopoulos, Athanassios, additional, Kaplani, Konstantina, additional, Moraiti, Maria, additional, van den Hengel, Lisa G., additional, Song, Ji-Ying, additional, Bleijerveld, Onno B., additional, Nieuwenhuis, Joppe, additional, Heidebrecht, Tatjana, additional, Henneman, Linda, additional, Moutin, Marie-Jo, additional, Barisic, Marin, additional, Taraviras, Stavros, additional, Perrakis, Anastassis, additional, and Brummelkamp, Thijn R., additional

Published
2022
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29. MYC promotes immune-suppression in TNBC via inhibition of IFN signaling

Author

Zimmerli, Dario, primary, Brambillasca, Chiara S, additional, Talens, Francien, additional, Bhin, Jinhyuk, additional, Bhattacharya, Arkajyoti, additional, Joosten, Stacey E.P., additional, Da Silva, Ana Moises, additional, Wellenstein, Max D., additional, Kersten, Kelly, additional, de Boo, Mart, additional, Roorda, Maurits, additional, Henneman, Linda, additional, de Bruijn, Roebi, additional, Annunziato, Stefano, additional, van der Burg, Eline, additional, Drenth, Anne Paulien, additional, Lutz, Catrin, additional, van de Ven, Marieke, additional, Wessels, Lodewyk, additional, de Visser, Karin, additional, Zwart, Wilbert, additional, Fehrmann, Rudolf S.N., additional, van Vugt, Marcel A.T.M., additional, and Jonkers, Jos, additional

Published
2021
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30. In situCRISPR‐Cas9 base editing for the development of genetically engineered mouse models of breast cancer

Author

Annunziato, Stefano, primary, Lutz, Catrin, additional, Henneman, Linda, additional, Bhin, Jinhyuk, additional, Wong, Kim, additional, Siteur, Bjørn, additional, Gerwen, Bas, additional, Korte‐Grimmerink, Renske, additional, Zafra, Maria Paz, additional, Schatoff, Emma M, additional, Drenth, Anne Paulien, additional, der Burg, Eline, additional, Eijkman, Timo, additional, Mukherjee, Siddhartha, additional, Boroviak, Katharina, additional, Wessels, Lodewyk FA, additional, de Ven, Marieke, additional, Huijbers, Ivo J, additional, Adams, David J, additional, Dow, Lukas E, additional, and Jonkers, Jos, additional

Published
2020
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31. Truncated FGFR2is a clinically actionable oncogene in multiple cancers

Author

Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M., Rolfs, Frank, Lutz, Catrin, Lee, Jessica K., Klarenbeek, Sjoerd, Silverman, Ian M., Annunziato, Stefano, Chan, Chang S., Piersma, Sander R., Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R., Riedlinger, Gregory M., Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H., Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R., Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K., Ross, Jeffrey S., van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M., Burn, Timothy C., Jimenez, Connie R., Ganesan, Shridar, Wessels, Lodewyk F. A., and Jonkers, Jos

Abstract

Somatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer1. However, clinical responses to FGFR inhibitors have remained variable1–9, emphasizing the need to better understand which FGFR2alterations are oncogenic and therapeutically targetable. Here we apply transposon-based screening10,11and tumour modelling in mice12,13, and find that the truncation of exon 18 (E18) of Fgfr2is a potent driver mutation. Human oncogenomic datasets revealed a diverse set of FGFR2alterations, including rearrangements, E1–E17 partial amplifications, and E18 nonsense and frameshift mutations, each causing the transcription of E18-truncated FGFR2(FGFR2ΔE18). Functional in vitro and in vivo examination of a compendium of FGFR2ΔE18and full-length variants pinpointed FGFR2-E18 truncation as single-driver alteration in cancer. By contrast, the oncogenic competence of FGFR2full-length amplifications depended on a distinct landscape of cooperating driver genes. This suggests that genomic alterations that generate stable FGFR2ΔE18variants are actionable therapeutic targets, which we confirmed in preclinical mouse and human tumour models, and in a clinical trial. We propose that cancers containing any FGFR2variant with a truncated E18 should be considered for FGFR-targeted therapies.

Published
2022
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32. Abstract A01: Somatic engineering of the mammary gland for the development of novel mouse models of triple-negative breast cancer

Author

Annunziato, Stefano, primary, Ruiter, Julian R. de, additional, Brambillasca, Chiara S., additional, Kas, Sjors M., additional, Ferrante, Federica, additional, Lutz, Catrin, additional, Siteur, Bjorn, additional, Gerwen, Bas van, additional, Ven, Marieke van de, additional, Miltenburg, Martine H. van, additional, Henneman, Linda, additional, and Jonkers, Jos, additional

Published
2018
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34. TRPM7 maintains progenitor-like features of neuroblastoma cells:Implications for metastasis formation

Author

Middelbeek, Jeroen, Visser, Daan, Henneman, Linda, Kamermans, Alwin, Kuipers, Arthur J., Hoogerbrugge, Peter M., Jalink, Kees, and van Leeuwen, Frank N.

Abstract

Neuroblastoma is an embryonal tumor derived from poorly differentiated neural crest cells. Current research is aimed at identifying the molecular mechanisms that maintain the progenitor state of neuroblastoma cells and to develop novel therapeutic strategies that induce neuroblastoma cell differentiation. Mechanisms controlling neural crest development are typically dysregulated during neuroblastoma progression, and provide an appealing starting point for drug target discovery. Transcriptional programs involved in neural crest development act as a context dependent gene regulatory network. In addition to BMP, Wnt and Notch signaling, activation of developmental gene expression programs depends on the physical characteristics of the tissue microenvironment. TRPM7, a mechanically regulated TRP channel with kinase activity, was previously found essential for embryogenesis and the maintenance of undifferentiated neural crest progenitors. Hence, we hypothesized that TRPM7 may preserve progenitor-like, metastatic features of neuroblastoma cells. Using multiple neuroblastoma cell models, we demonstrate that TRPM7 expression closely associates with the migratory and metastatic properties of neuroblastoma cells in vitro and in vivo. Moreover, microarray-based expression profiling on control and TRPM7 shRNA transduced neuroblastoma cells indicates that TRPM7 controls a developmental transcriptional program involving the transcription factor SNAI2. Overall, our data indicate that TRPM7 contributes to neuroblastoma progression by maintaining progenitor-like features.

Published
2015

37. TRPM7 Is Required for Breast Tumor Cell Metastasis

Author

Middelbeek, Jeroen, primary, Kuipers, Arthur J., additional, Henneman, Linda, additional, Visser, Daan, additional, Eidhof, Ilse, additional, van Horssen, Remco, additional, Wieringa, Bé, additional, Canisius, Sander V., additional, Zwart, Wilbert, additional, Wessels, Lodewyk F., additional, Sweep, Fred C.G.J., additional, Bult, Peter, additional, Span, Paul N., additional, van Leeuwen, Frank N., additional, and Jalink, Kees, additional

Published
2012
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40. Publisher Correction: Truncated FGFR2is a clinically actionable oncogene in multiple cancers

Author

Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M., Rolfs, Frank, Lutz, Catrin, Lee, Jessica K., Klarenbeek, Sjoerd, Silverman, Ian M., Annunziato, Stefano, Chan, Chang S., Piersma, Sander R., Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R., Riedlinger, Gregory M., Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H., Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R., Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K., Ross, Jeffrey S., van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M., Burn, Timothy C., Jimenez, Connie R., Ganesan, Shridar, Wessels, Lodewyk F. A., and Jonkers, Jos

Published
2022
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41. Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer

Author

Jonkers, Jos, Huijbers, Ivo J, Schlicker, Andreas, Jaspers, Janneke E, Szuhai, Karoly, Bin Ali, Rahmen, Van Miltenburg, Martine H, Braumuller, Tanya M, De Korte-Grimmerink, Renske, Pritchard, Colin, Henneman, Linda, Michalak, Ewa M, Berns, Anton, Rottenberg, Sven, Gogola, Ewa, and Drenth, Anne Paulien

Subjects
endocrine system diseases, 630 Agriculture, polycyclic compounds, skin and connective tissue diseases, 3. Good health
Abstract

Metaplastic breast carcinoma (MBC) is a rare histological breast cancer subtype characterized by mesenchymal elements and poor clinical outcome. A large fraction of MBCs harbor defects in breast cancer 1 (BRCA1). As BRCA1 deficiency sensitizes tumors to DNA cross-linking agents and poly(ADP-ribose) polymerase (PARP) inhibitors, we sought to investigate the response of BRCA1-deficient MBCs to the PARP inhibitor olaparib. To this end, we established a genetically engineered mouse model (GEMM) for BRCA1-deficient MBC by introducing the MET proto-oncogene into a BRCA1-associated breast cancer model, using our novel female GEMM ES cell (ESC) pipeline. In contrast to carcinomas, BRCA1-deficient mouse carcinosarcomas resembling MBC show intrinsic resistance to olaparib caused by increased P-glycoprotein (Pgp) drug efflux transporter expression. Indeed, resistance could be circumvented by using another PARP inhibitor, AZD2461, which is a poor Pgp substrate. These preclinical findings suggest that patients with BRCA1-associated MBC may show poor response to olaparib and illustrate the value of GEMM-ESC models of human cancer for evaluation of novel therapeutics.

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