Transcriptional targets of Drosophila JAK/STAT pathway signalling as effectors of haematopoietic tumour formation.
Although many signal transduction pathways have been implicated in the development of human disease, the identification of pathway targets and the biological processes that mediate disease progression remains challenging. One such disease-related pathway is the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) cascade whose constitutive misactivation by the JAK2 V617F mutation underlies most human myeloproliferative disorders. Here, we use transcript profiling of Drosophila haemocyte-like cells to identify JAK/STAT target genes, combined with an in vivo model for JAK-induced blood cell overproliferation, to identify the main effectors required for haematopoietic tumour development. The identified human homologues of the Drosophila effectors were tested for potential V617F-mediated transcriptional regulation in human HeLa cells and compared with small interfering RNA-derived data, quantify their role in regulating the proliferation of cancer-derived cell lines. Such an inter-species approach is an effective way to identify factors with conserved functions that might be central to human disease.
Bina
Samira
S
MRC Centre for Developmental & Biomedical Genetics, The University of Sheffield, Western Bank, Sheffield, UK.
Wright
Victoria M
VM
Fisher
Katherine H
KH
Milo
Marta
M
Zeidler
Martin P
MP
D000818:Animals; D049109:Cell Proliferation; D016000:Cluster Analysis; D004331:Drosophila melanogaster; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006434:Hemocytes / Q000166:cytology; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
D034741:RNA, Small Interfering; D050791:STAT Transcription Factors; D053612:Janus Kinases