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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...

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Main Authors: Munkhbaatar, Enkhtsetseg (Author) , Dietzen, Michelle (Author) , Agrawal, Deepti (Author) , Anton, Martina (Author) , Jesinghaus, Moritz (Author) , Boxberg, Melanie (Author) , Pfarr, Nicole (Author) , Bidola, Pidassa (Author) , Uhrig, Sebastian (Author) , Höckendorf, Ulrike (Author) , Meinhardt, Anna-Lena (Author) , Wahida, Adam (Author) , Heid, Irina (Author) , Braren, Rickmer (Author) , Mishra, Ritu (Author) , Warth, Arne (Author) , Muley, Thomas (Author) , Poh, Patrina S. P. (Author) , Wang, Xin (Author) , Fröhling, Stefan (Author) , Steiger, Katja (Author) , Slotta-Huspenina, Julia (Author) , van Griensven, Martijn (Author) , Pfeiffer, Franz (Author) , Lange, Sebastian (Author) , Rad, Roland (Author) , Spella, Magda (Author) , Stathopoulos, Georgios T. (Author) , Ruland, Jürgen (Author) , Bassermann, Florian (Author) , Weichert, Wilko (Author) , Strasser, Andreas (Author) , Branca, Caterina (Author) , Heikenwälder, Mathias (Author) , Swanton, Charles (Author) , McGranahan, Nicholas (Author) , Jost, Philipp J. (Author)
Format: Article (Journal)
Language:English
Published: 10 September 2020
In: Nature Communications
Year: 2020, Volume: 11, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-020-18372-1
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-020-18372-1
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-020-18372-1
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Author Notes:Enkhtsetseg Munkhbaatar, Michelle Dietzen, Deepti Agrawal, Martina Anton, Moritz Jesinghaus, Melanie Boxberg, Nicole Pfarr, Pidassa Bidola, Sebastian Uhrig, Ulrike Höckendorf, Anna-Lena Meinhardt, Adam Wahida, Irina Heid, Rickmer Braren, Ritu Mishra, Arne Warth, Thomas Muley, Patrina S.P. Poh, Xin Wang, Stefan Fröhling, Katja Steiger, Julia Slotta-Huspenina, Martijn van Griensven, Franz Pfeiffer, Sebastian Lange, Roland Rad, Magda Spella, Georgios T. Stathopoulos, Jürgen Ruland, Florian Bassermann, Wilko Weichert, Andreas Strasser, Caterina Branca, Mathias Heikenwalder, Charles Swanton, Nicholas McGranahan & Philipp J. Jost
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Summary: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.
Item Description:Gesehen am 10.03.2021
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-020-18372-1

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