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Series GSE147642 Query DataSets for GSE147642
Status Public on Apr 15, 2020
Title Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALKF1174L is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALKF1174L overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALKF1174L cooperates with oncogenic KrasG12D and loss of p53, well established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher-grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALKF1174L and is indispensable for ALKF1174L-driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials.
Overall design mRNA profiles of FACS-sorted tumor cells from ear cSCC from ALKF1174L Lgr5-CreERT2 mice, ALKF1174LKrasG12D Lgr5-CreERT2 mice and from sorted normal ear skin keratinocytes of cre negative siblings were produced in triplicate.
Contributor(s) Gualandi M, Iorio M, Engeler O, Serra-Roma A, Gasparre G, Schulte J, Hohl D, Shakhova O
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Submission date Mar 27, 2020
Last update date Apr 17, 2020
Contact name giancarlo russo
Organization name ETH/University of Zurich
Department Functional Genomics Center Zurich
Street address winterthurerstrasse 190
City Zurich
State/province Schweiz
ZIP/Postal code 8057
Country Switzerland
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (9)
GSM4437173 WT_1_sorted
GSM4437174 WT_4_sorted
GSM4437175 WT_5_sorted
BioProject PRJNA615866
SRA SRP254328

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE147642_RAW.tar 1.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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