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- Title
MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
- Authors
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
- Abstract
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. Cancer cells frequently harbour genetic aberrations that protect them from programmed cell death. Here, the authors show in non-small cell lung cancer that the anti-apoptotic gene MCL-1 is subject to copy number gains and that deletion of MCL-1 reduces tumour formation.
- Subjects
NON-small-cell lung carcinoma; APOPTOSIS; ADENOCARCINOMA; CELLULAR evolution; LUNGS
- Publication
Nature Communications, 2020, Vol 11, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-18372-1