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- W2000399084 abstract "Transforming growth factor beta (TGF-beta) signaling, which regulates multiple cellular processes including proliferation, apoptosis, and differentiation, plays an important but incompletely understood role in normal and cancerous tissues. For instance, although TGF-beta functions as a tumor suppressor in the premalignant stages of tumorigenesis, paradoxically, it also seems to act as a tumor promoter in advanced cancer leading to metastasis. The mechanisms by which TGF-beta elicits such diverse responses during cancer progression are still not entirely clear. As a first step toward understanding TGF-beta signaling quantitatively, we have developed a comprehensive, dynamic model of the canonical TGF-beta pathway via Smad transcription factors. By describing how an extracellular signal of the TGF-beta ligand is sensed by receptors and transmitted into the nucleus through intracellular Smad proteins, the model provides quantitative insight into how TGF-beta-induced responses are modulated and regulated. Subsequent model analysis shows that mechanisms associated with Smad activation by ligand-activated receptor, nuclear complex formation among Smad proteins, and inactivation of ligand-activated Smad (e.g., degradation, dephosphorylation) may be critical for regulating TGF-beta-targeted functional responses. The model was also used to predict dynamic characteristics of the Smad-mediated pathway in abnormal cells, from which we generated four testable hypotheses regarding potential mechanisms by which TGF-beta's tumor-suppressive roles may appear to morph into tumor-promotion during cancer progression." @default.
- W2000399084 created "2016-06-24" @default.
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- W2000399084 date "2009-03-01" @default.
- W2000399084 modified "2023-10-17" @default.
- W2000399084 title "Quantitative Modeling and Analysis of the Transforming Growth Factor β Signaling Pathway" @default.
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- W2000399084 doi "https://doi.org/10.1016/j.bpj.2008.11.050" @default.
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