Regulation of EMT by TGFβ in cancer.
Transforming growth factor-β (TGFβ) suppresses tumor formation since it inhibits cell growth and promotes apoptosis. However, in advanced cancers TGFβ elicits tumor promoting effects through its ability to induce epithelial-mesenchymal transition (EMT) which enhances invasiveness and metastasis; in addition, TGFβ exerts tumor promoting effects on non-malignant cells of the tumor, including suppression of immune surveillance and stimulation of angiogenesis. TGFβ promotes EMT by transcriptional and posttranscriptional regulation of a group of transcription factors that suppresses epithelial features, such as expression of components of cell junctions and polarity complexes, and enhances mesenchymal features, such as production of matrix molecules and several cytokines and growth factors that stimulate cell migration. The EMT program has certain similarities with the stem cell program. Inducers and effectors of EMT are interesting targets for the development of improved diagnosis, prognosis and therapy of cancer.
Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden. c-h.heldin@licr.uu.se
Carl-Henrik
CH
Heldin
Michael
M
Vanlandewijck
Aristidis
A
Moustakas
D000818:Animals; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta