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Identification of Ankrd35 as a mediator of cisplatin response in non-small cell lung cancer by ex vivo 3D screening of primary tumor spheroids

ABSTRACT: Using pooled shRNA libraries, we performed a focused screen of 515 genes selected for involvement in response to chemotherapy. The results of this screen confirmed Notch signaling is important for primary tumor cell survival and the importance of key DNA damage response regulators for platinum-induced damage, including Ercc1. Our results establish Ankrd35, a previously uncharacterized ankyrin repeat domain protein, as an important mediator of chemoresistance in ex vivo cultures.

ORGANISM(S): Mus musculus

PROVIDER: GSE136316 | GEO | 2021/11/11

REPOSITORIES: GEO

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Identification of Ankrd35 as a mediator of cisplatin response in non-small cell lung cancer by in vivo screening of murine tumor derived xenografts

Project description:Using a pooled shRNA library, we performed a focused screen of 81 shRNAs selected for involvement in response to chemotherapy in an ex vivo 3D primary tumor cell culture system. Our results establish Ankrd35, a previously uncharacterized ankyrin repeat domain protein, as an important mediator of chemoresistance in vivo.

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Project description:The XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA damage and interstrand crosslinks. Here we have engineered a severe mutation in Ercc1 gene (in which the last 7 amino acids are missing; named as "Ercc1-delta") leading to extreme sensitivity to DNA crosslinks and progeria.To investigate whether a disturbance in growth and metabolism could explain the pronounced accelerated organismal deterioration seen in Ercc1 delta mice, we evaluated the liver transcriptome of 16-week-old wt and mutant mice (n=6). At this age, the Ercc1-delta mice have not yet become cachectic.

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Identification of Ankrd35 as a mediator of cisplatin response in non-small cell lung cancer by ex vivo 3D screening of primary tumor spheroids

Project description:This SuperSeries is composed of the SubSeries listed below.

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