Oncogenic cooperation between SOCS family proteins and EGFR identified using a Drosophila epithelial transformation model.
MicroRNAs (miRNAs) are emerging as cooperating factors that promote the activity of oncogenes in tumor formation and disease progression. This poses the challenge of identifying the miRNA targets responsible for these interactions. In this study, we identify the growth regulatory miRNA bantam and its target, Socs36E, as cooperating factors in EGFR-driven tumorigenesis and metastasis in a Drosophila model of epithelial transformation. bantam promotes growth by limiting expression of Socs36E, which functions as a negative growth regulator. Socs36E has only a modest effect on growth on its own, but behaves as a tumor suppressor in combination with EGFR activation. The human ortholog of SOCS36E, SOCS5, behaves as a candidate tumor suppressor in cellular transformation in cooperation with EGFR/RAS pathway activation.
Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Héctor
H
Herranz
Xin
X
Hong
Nguyen Thanh
NT
Hung
P Mathijs
PM
Voorhoeve
Stephen M
SM
Cohen
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D035683:MicroRNAs; D018010:Receptors, Invertebrate Peptide; C460659:Socs36E protein, Drosophila; D050826:Suppressor of Cytokine Signaling Proteins; D025521:Tumor Suppressor Proteins; C471146:bantam microRNA, Drosophila; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D018631:ras Proteins