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1. GREM1 is required to maintain cellular heterogeneity in pancreatic cancer

Author

Lan, Linxiang, Evan, Theodore, Li, Huafu, Hussain, Aasia, Ruiz, E. Josue, Zaw Thin, May, Ferreira, Rute M. M., Ps, Hari, Riising, Eva M., Zen, Yoh, Almagro, Jorge, Ng, Kevin W., Soro-Barrio, Pablo, Nelson, Jessica, Koifman, Gabriela, Carvalho, Joana, Nye, Emma L., He, Yulong, Zhang, Changhua, Sadanandam, Anguraj, and Behrens, Axel

Published
2022
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2. GREM1 is required to maintain cellular heterogeneity in pancreatic cancer

Author

Lan, Linxiang, Evan, Theodore, Li, Huafu, Hussain, Aasia, Ruiz, E. Josue, Zaw Thin, May, Ferreira, Rute M. M., Ps, Hari, Riising, Eva M., Zen, Yoh, Almagro, Jorge, Ng, Kevin W., Soro-Barrio, Pablo, Nelson, Jessica, Koifman, Gabriela, Carvalho, Joana, Nye, Emma L., He, Yulong, Zhang, Changhua, Sadanandam, Anguraj, and Behrens, Axel

Abstract

Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations1–4. Cellular heterogeneity in PDAC is an important feature in disease subtype specification3–5, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM16,7as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse. Grem1inactivation in established PDAC in mice resulted in a direct conversion of epithelial into mesenchymal PDAC cells within days, suggesting that persistent GREM1 activity is required to maintain the epithelial PDAC subpopulations. By contrast, Grem1overexpression caused an almost complete ‘epithelialization’ of highly mesenchymal PDAC, indicating that high GREM1 activity is sufficient to revert the mesenchymal fate of PDAC cells. Mechanistically, Grem1was highly expressed in mesenchymal PDAC cells and inhibited the expression of the epithelial–mesenchymal transition transcription factors Snai1(also known as Snail) and Snai2(also known as Slug) in the epithelial cell compartment, therefore restricting epithelial–mesenchymal plasticity. Thus, constant suppression of BMP activity is essential to maintain epithelial PDAC cells, indicating that the maintenance of the cellular heterogeneity of pancreatic cancer requires continuous paracrine signalling elicited by a single soluble factor.

Published
2024
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3. USP28 deletion and small-molecule inhibition destabilizes c-MYC and elicits regression of squamous cell lung carcinoma

Author

Ruiz, E Josue, primary, Pinto-Fernandez, Adan, additional, Turnbull, Andrew P, additional, Lan, Linxiang, additional, Charlton, Thomas M, additional, Scott, Hannah C, additional, Damianou, Andreas, additional, Vere, George, additional, Riising, Eva M, additional, Da Costa, Clive, additional, Krajewski, Wojciech W, additional, Guerin, David, additional, Kearns, Jeffrey D, additional, Ioannidis, Stephanos, additional, Katz, Marie, additional, McKinnon, Crystal, additional, O'Connell, Jonathan, additional, Moncaut, Natalia, additional, Rosewell, Ian, additional, Nye, Emma, additional, Jones, Neil, additional, Heride, Claire, additional, Gersch, Malte, additional, Wu, Min, additional, Dinsmore, Christopher J, additional, Hammonds, Tim R, additional, Kim, Sunkyu, additional, Komander, David, additional, Urbe, Sylvie, additional, Clague, Michael J, additional, Kessler, Benedikt M, additional, and Behrens, Axel, additional

Published
2021
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4. Author response: USP28 deletion and small-molecule inhibition destabilizes c-MYC and elicits regression of squamous cell lung carcinoma

Author

Ruiz, E Josue, primary, Pinto-Fernandez, Adan, additional, Turnbull, Andrew P, additional, Lan, Linxiang, additional, Charlton, Thomas M, additional, Scott, Hannah C, additional, Damianou, Andreas, additional, Vere, George, additional, Riising, Eva M, additional, Da Costa, Clive, additional, Krajewski, Wojciech W, additional, Guerin, David, additional, Kearns, Jeffrey D, additional, Ioannidis, Stephanos, additional, Katz, Marie, additional, McKinnon, Crystal, additional, O'Connell, Jonathan, additional, Moncaut, Natalia, additional, Rosewell, Ian, additional, Nye, Emma, additional, Jones, Neil, additional, Heride, Claire, additional, Gersch, Malte, additional, Wu, Min, additional, Dinsmore, Christopher J, additional, Hammonds, Tim R, additional, Kim, Sunkyu, additional, Komander, David, additional, Urbe, Sylvie, additional, Clague, Michael J, additional, Kessler, Benedikt M, additional, and Behrens, Axel, additional

Published
2021
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5. Verification of CRISPR editing and finding transgenic inserts by Xdrop indirect sequence capture followed by short- and long-read sequencing

Author

Blondal, Thorarinn, primary, Gamba, Cristina, additional, Møller Jagd, Lea, additional, Su, Ling, additional, Demirov, Dimiter, additional, Guo, Shuang, additional, Johnston, Camille M., additional, Riising, Eva M., additional, Wu, Xiaolin, additional, Mikkelsen, Marie J., additional, Szabova, Ludmila, additional, and Mouritzen, Peter, additional

Published
2021
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6. USP28 deletion and small molecule inhibition destabilises c-Myc and elicits regression of squamous cell lung carcinoma

Author

Ruiz, E. Josue, primary, Pinto-Fernandez, Adan, additional, Turnbull, Andrew P., additional, Lan, Linxiang, additional, Charlton, Thomas M., additional, Scott, Hannah Claire, additional, Damianou, Andreas, additional, Vere, George, additional, Riising, Eva M., additional, Da Costa, Clive, additional, Krajewski, Wojciech W., additional, Guerin, David, additional, Kearns, Jeffrey, additional, Ioannidis, Stephanos, additional, Katz, Marie, additional, McKinnon, Crystal, additional, O’Connell, Jonathan C., additional, Moncaut, Natalia, additional, Rosewell, Ian, additional, Nye, Emma, additional, Jones, Neil, additional, Heride, Claire, additional, Gersch, Malte, additional, Wu, Min, additional, Dinsmore, Christopher J., additional, Hammonds, Tim R., additional, Kim, Sunkyu, additional, Komander, David, additional, Urbé, Sylvie, additional, Clague, Michael J., additional, Kessler, Benedikt M., additional, and Behrens, Axel, additional

Published
2020
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7. Verification of CRISPR editing and finding transgenic inserts by Xdrop™ Indirect sequence capture followed by short- and long- read sequencing

Author

Thorarinn, Blondal, primary, Cristina, Gamba, additional, Møller, Jagd Lea, additional, Ling, Su, additional, Dimiter, Demirov, additional, Shuang, Guo, additional, Johnston, Camille M., additional, Riising, Eva M., additional, Xiaolin, Wu, additional, Mikkelsen, Marie J., additional, Ludmila, Szabova, additional, and Peter, Mouritzen, additional

Published
2020
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9. Functional Screening Identifies miRNAs Influencing Apoptosis and Proliferation in Colorectal Cancer

Author

Christensen, Lise Lotte, primary, Holm, Anja, additional, Rantala, Juha, additional, Kallioniemi, Olli, additional, Rasmussen, Mads H., additional, Ostenfeld, Marie S., additional, Dagnaes-Hansen, Frederik, additional, Øster, Bodil, additional, Schepeler, Troels, additional, Tobiasen, Heidi, additional, Thorsen, Kasper, additional, Sieber, Oliver M., additional, Gibbs, Peter, additional, Lamy, Philippe, additional, Hansen, Torben F., additional, Jakobsen, Anders, additional, Riising, Eva M., additional, Helin, Kristian, additional, Lubinski, Jan, additional, Hagemann-Madsen, Rikke, additional, Laurberg, Søren, additional, Ørntoft, Torben F., additional, and Andersen, Claus L., additional

Published
2014
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