2026-06-14T03:52:41Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/197562024-11-29T13:50:36Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Rosigkeit, Sebastian
author
Kruchem, Marie
author
Thies, Dorothe
author
Kreft, Andreas
author
Eichler, Emma
author
Boegel, Sebastian
author
Jansky, Sandrine
author
Siegl, Dominik
author
Kaps, Leonard
author
Pickert, Geethanjali
author
Haehnel, Patricia
author
Kindler, Thomas
author
Hartwig, Udo F
author
Guerra, Carmen
author
Barbacid, Mariano
author
Schuppan, Detlef
author
Bockamp, Ernesto
funder
German Research Foundation (DFG)
funder
ERAPerMed
funder
Stiftung Rheinland-Pfalz fur Innovation
2024-06-12T09:46:01Z
2024-06-12T09:46:01Z
2021-11-01
Int J Cancer. 2021 ;149(9):1670-1682
10.1002/ijc.33756
1097-0215
International journal of cancer
34331774
http://hdl.handle.net/20.500.12105/19756
Accumulating evidence suggests that both the nature of oncogenic lesions and the cell-of-origin can strongly influence cancer histopathology, tumor aggressiveness and response to therapy. Although oncogenic Kras expression and loss of Trp53 tumor suppressor gene function have been demonstrated to initiate murine lung adenocarcinomas (LUADs) in alveolar type II (AT2) cells, clear evidence that Club cells, representing the second major subset of lung epithelial cells, can also act as cells-of-origin for LUAD is lacking. Equally, the exact anatomic location of Club cells that are susceptible to Kras transformation and the resulting tumor histotype remains to be established. Here, we provide definitive evidence for Club cells as progenitors for LUAD. Using in vivo lineage tracing, we find that a subset of Kras12V -expressing and Trp53-deficient Club cells act as precursors for LUAD and we define the stepwise trajectory of Club cell-initiated tumors leading to lineage marker conversion and aggressive LUAD. Our results establish Club cells as cells-of-origin for LUAD and demonstrate that Club cell-initiated tumors have the potential to develop aggressive LUAD.
eng
Definitive evidence for Club cells as progenitors for mutant Kras/Trp53-deficient lung cancer.
other
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URL
https://repisalud.isciii.es/bitstreams/b8688faf-f257-4954-a4ad-71fe9f33852f/download
File
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application/pdf
DefinitiveevidenceforClubcells_2021.pdf
URL
https://repisalud.isciii.es/bitstreams/74e91057-6b47-49e4-8c00-afc60fa9c988/download
File
MD5
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text/plain
DefinitiveevidenceforClubcells_2021.pdf.txt