Malignant transformation but not normal cell growth depends on signal transducer and activator of transcription 3.
Signal transducer and activator of transcription 3 (STAT3) has been indirectly implicated in numerous fundamental cellular processes, including proliferation, survival, and differentiation. We provide genetic evidence from studies of STAT3-null cells that STAT3 is dispensable for normal growth of mouse fibroblasts in culture. STAT3 contributed to the full induction of some (typified by c-fos) but not all (typified by c-myc) immediate early gene expression, but STAT3-independent processes were sufficient to support full cell growth and survival. However, STAT3 was required to manifest a transformed state following expression of v-src, and STAT3-null cells were impaired for anchorage-independent growth as colonies in soft agar and as tumors in mice. The data suggest that STAT3 mediates the maintenance of focal adhesion kinase activity in the absence of cell adhesion by suppressing the action of an inhibitory phosphatase.
Department of Pathology and New York University Cancer Institute, New York University School of Medicine, New York, New York 10016, USA.
Karni
K
Schlessinger
David E
DE
Levy
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005786:Gene Expression Regulation; D016762:Genes, fos; D016391:Genes, src; D051379:Mice; D008807:Mice, Inbred BALB C; D015688:Oncogene Protein pp60(v-src) / Q000096:biosynthesis / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics*
D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); C496051:Ptk2 protein, mouse