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MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role o...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484793/ https://www.ncbi.nlm.nih.gov/pubmed/32913197 http://dx.doi.org/10.1038/s41467-020-18372-1 |
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| author | Munkhbaatar, Enkhtsetseg Dietzen, Michelle Agrawal, Deepti Anton, Martina Jesinghaus, Moritz Boxberg, Melanie Pfarr, Nicole Bidola, Pidassa Uhrig, Sebastian Höckendorf, Ulrike Meinhardt, Anna-Lena Wahida, Adam Heid, Irina Braren, Rickmer Mishra, Ritu Warth, Arne Muley, Thomas Poh, Patrina S. P. Wang, Xin Fröhling, Stefan Steiger, Katja Slotta-Huspenina, Julia van Griensven, Martijn Pfeiffer, Franz Lange, Sebastian Rad, Roland Spella, Magda Stathopoulos, Georgios T. Ruland, Jürgen Bassermann, Florian Weichert, Wilko Strasser, Andreas Branca, Caterina Heikenwalder, Mathias Swanton, Charles McGranahan, Nicholas Jost, Philipp J. |
| author_facet | Munkhbaatar, Enkhtsetseg Dietzen, Michelle Agrawal, Deepti Anton, Martina Jesinghaus, Moritz Boxberg, Melanie Pfarr, Nicole Bidola, Pidassa Uhrig, Sebastian Höckendorf, Ulrike Meinhardt, Anna-Lena Wahida, Adam Heid, Irina Braren, Rickmer Mishra, Ritu Warth, Arne Muley, Thomas Poh, Patrina S. P. Wang, Xin Fröhling, Stefan Steiger, Katja Slotta-Huspenina, Julia van Griensven, Martijn Pfeiffer, Franz Lange, Sebastian Rad, Roland Spella, Magda Stathopoulos, Georgios T. Ruland, Jürgen Bassermann, Florian Weichert, Wilko Strasser, Andreas Branca, Caterina Heikenwalder, Mathias Swanton, Charles McGranahan, Nicholas Jost, Philipp J. |
| author_sort | Munkhbaatar, Enkhtsetseg |
| collection | PubMed |
| description | Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically. |
| format | Online Article Text |
| id | pubmed-7484793 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-74847932020-09-21 MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically Munkhbaatar, Enkhtsetseg Dietzen, Michelle Agrawal, Deepti Anton, Martina Jesinghaus, Moritz Boxberg, Melanie Pfarr, Nicole Bidola, Pidassa Uhrig, Sebastian Höckendorf, Ulrike Meinhardt, Anna-Lena Wahida, Adam Heid, Irina Braren, Rickmer Mishra, Ritu Warth, Arne Muley, Thomas Poh, Patrina S. P. Wang, Xin Fröhling, Stefan Steiger, Katja Slotta-Huspenina, Julia van Griensven, Martijn Pfeiffer, Franz Lange, Sebastian Rad, Roland Spella, Magda Stathopoulos, Georgios T. Ruland, Jürgen Bassermann, Florian Weichert, Wilko Strasser, Andreas Branca, Caterina Heikenwalder, Mathias Swanton, Charles McGranahan, Nicholas Jost, Philipp J. Nat Commun Article Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically. Nature Publishing Group UK 2020-09-10 /pmc/articles/PMC7484793/ /pubmed/32913197 http://dx.doi.org/10.1038/s41467-020-18372-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Munkhbaatar, Enkhtsetseg Dietzen, Michelle Agrawal, Deepti Anton, Martina Jesinghaus, Moritz Boxberg, Melanie Pfarr, Nicole Bidola, Pidassa Uhrig, Sebastian Höckendorf, Ulrike Meinhardt, Anna-Lena Wahida, Adam Heid, Irina Braren, Rickmer Mishra, Ritu Warth, Arne Muley, Thomas Poh, Patrina S. P. Wang, Xin Fröhling, Stefan Steiger, Katja Slotta-Huspenina, Julia van Griensven, Martijn Pfeiffer, Franz Lange, Sebastian Rad, Roland Spella, Magda Stathopoulos, Georgios T. Ruland, Jürgen Bassermann, Florian Weichert, Wilko Strasser, Andreas Branca, Caterina Heikenwalder, Mathias Swanton, Charles McGranahan, Nicholas Jost, Philipp J. MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| title | MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| title_full | MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| title_fullStr | MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| title_full_unstemmed | MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| title_short | MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| title_sort | mcl-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484793/ https://www.ncbi.nlm.nih.gov/pubmed/32913197 http://dx.doi.org/10.1038/s41467-020-18372-1 |
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