Role of STAT3 in in vitro transformation triggered by TRK oncogenes.
TRK oncoproteins are chimeric versions of the NTRK1/NGF receptor and display constitutive tyrosine kinase activity leading to transformation of NIH3T3 cells and neuronal differentiation of PC12 cells. Signal Transducer and Activator of Transcription (STAT) 3 is activated in response to cytokines and growth factors and it has been recently identified as a novel signal transducer for TrkA, mediating the functions of NGF in nervous system. In this paper we have investigated STAT3 involvement in signalling induced by TRK oncogenes. We showed that TRK oncogenes trigger STAT3 phosphorylation both on Y705 and S727 residues and STAT3 transcriptional activity. MAPK pathway was involved in the induction of STAT3 phosphorylation. Interestingly, we have shown reduced STAT3 protein level in NIH3T3 transformed foci expressing TRK oncogenes. Overall, we have unveiled a dual role for STAT3 in TRK oncogenes-induced NIH3T3 transformation: i) decreased STAT3 protein levels, driven by TRK oncoproteins activity, are associated to morphological transformation; ii) residual STAT3 transcriptional activity is required for cell growth.
Miranda
Claudia
C
Operative Unit Molecular Mechanisms, Department of Experimental Oncology and Molecular Medicine, IRCCS Foundation, Istituto Nazionale dei Tumori, Milan, Italy. claudia.miranda@istitutotumori.mi.it
Fumagalli
Tiziana
T
Anania
Maria Chiara
MC
Vizioli
Maria Grazia
MG
Pagliardini
Sonia
S
Pierotti
Marco A
MA
Greco
Angela
A
D000818:Animals; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000378:metabolism*; D009857:Oncogenes; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D015513:Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C065400:oncogene protein trk