Phospho-specific Smad3 signaling: impact on breast oncogenesis.
Members of the TGFβ superfamily are known to exert a myriad of physiologic and pathologic growth controlling influences on mammary development and oncogenesis. In epithelial cells, TGFβ signaling inhibits cell growth through cytostatic and pro-apoptotic activities but can also induce cancer cell EMT and, thus, has a dichotomous role in breast cancer biology. Mechanisms governing this switch are the subject of active investigation. Smad3 is a critical intracellular mediator of TGFβ signaling regulated through phosphorylation by the TGFβ receptor complex at the C terminus. Smad3 is also a substrate for several other kinases that phosphorylate additional sites within the Smad protein. This discovery has expanded the understanding of the significance and complexity of TGFβ signaling through Smads. This review highlights recent advances revealing the critical role of phospho-specific Smad3 in malignancy and illustrates the potential prognostic and therapeutic impact of Smad3 phospho-isoforms in breast cancer.
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Elizabeth
E
Tarasewicz
Jacqueline S
JS
Jeruss
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D051900:Smad3 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta