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Status |
Public on Jun 27, 2015 |
Title |
Oncogene-dependent regulation of tumor cells via stromal reciprocal signalling |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Cancer is a heterocellular disease composed of tumor cells and stromal cells. Although stromal cells are known to regulate cancer progression, oncogene-dependent signalling through heterocellular cancer systems remains poorly elucidated. Here, we describe KRASG12D-dependent ‘reciprocal’ signalling across tumor and stromal Pancreatic Ductal Adenocarcinoma (PDA) cells. Heterocellular multivariate phosphoproteomics demonstrates how an oncogenic cue (KRASG12D), a trans-cellular signal (SHH), and stromal cells drive a reciprocal response in tumor cells. KRASG12D-dependent reciprocal signalling regulates the tumor cell phosphoproteome, total proteome, and mitochondria activity via an IGFR1/AXL-AKT axis. The reciprocal KRASG12D signalling state requires a heterocellular context and is unreachable by cell-autonomous oncogenic KRAS alone. These findings provide evidence that oncogenic KRAS regulates tumor cells via heterocellular reciprocation.
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Overall design |
Comparison between FACS resolved iKRAS cells (previously in co-culture with PSCs) pertubed with a SHH antibody
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Contributor(s) |
Tape CJ, Ling S, Worboys JD, Leong HS, McMahon KM, Norrie IC, Miller CJ, Lauffenburger DA, Jørgensen C |
Citation missing |
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Submission date |
Jun 27, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Hui Sun Leong |
E-mail(s) |
HuiSun.Leong@cruk.manchester.ac.uk
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Organization name |
Cancer Research UK Manchester Institute
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Department |
The University of Manchester
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Lab |
Computational Biology Support Team
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Street address |
Wilmslow Road
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City |
Manchester |
ZIP/Postal code |
M20 4BX |
Country |
United Kingdom |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (8)
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Relations |
BioProject |
PRJNA288372 |
SRA |
SRP059937 |