TY - JOUR
T1 - Transforming growth factor-β signal transduction in epithelial cells
AU - Yue, Jianbo
AU - Mulder, Kathleen M.
N1 - Funding Information:
This work was supported by National Institution of Health Grants CA51452, CA54816, CA68444, and CA90765 awarded to K.M.M.
PY - 2001
Y1 - 2001
N2 - Transforming growth factor (TGF)-β is a natural and potent growth inhibitor of a variety of cell types, including epithelial, endothelial, and hematopoietic cells. The ability of TGF-β to potently inhibit the growth of many solid tumors of epithelial origin, including breast and colon carcinomas, is of particular interest. However, many solid tumor cells become refractory to the growth inhibitory effects of TGF-β due to defects in TGF-β signaling pathways. In addition, TGF-β may stimulate the invasiveness of tumor cells via the paracrine effects of TGF-β. Accordingly, in order to develop more effective anticancer therapeutics, it is necessary to determine the TGF-β signal transduction pathways underlying the growth inhibitory effects and other cellular effects of TGF-β in normal epithelial cells. Thus far, two primary signaling cascades downstream of the TGF-β receptors have been elucidated, the Sma and mothers against decapentaplegic homologues and the Ras/mitogen-activated protein kinase pathways. The major objective of this review is to summarize TGF-β signaling in epithelial cells, focusing on recent advances involving the Sma and mothers against decapentaplegic homologues and Ras/mitogen-activated protein kinase pathways. This review is particularly timely in that it provides a comprehensive summary of both signal transduction mechanisms and the cell cycle effects of TGF-β.
AB - Transforming growth factor (TGF)-β is a natural and potent growth inhibitor of a variety of cell types, including epithelial, endothelial, and hematopoietic cells. The ability of TGF-β to potently inhibit the growth of many solid tumors of epithelial origin, including breast and colon carcinomas, is of particular interest. However, many solid tumor cells become refractory to the growth inhibitory effects of TGF-β due to defects in TGF-β signaling pathways. In addition, TGF-β may stimulate the invasiveness of tumor cells via the paracrine effects of TGF-β. Accordingly, in order to develop more effective anticancer therapeutics, it is necessary to determine the TGF-β signal transduction pathways underlying the growth inhibitory effects and other cellular effects of TGF-β in normal epithelial cells. Thus far, two primary signaling cascades downstream of the TGF-β receptors have been elucidated, the Sma and mothers against decapentaplegic homologues and the Ras/mitogen-activated protein kinase pathways. The major objective of this review is to summarize TGF-β signaling in epithelial cells, focusing on recent advances involving the Sma and mothers against decapentaplegic homologues and Ras/mitogen-activated protein kinase pathways. This review is particularly timely in that it provides a comprehensive summary of both signal transduction mechanisms and the cell cycle effects of TGF-β.
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U2 - 10.1016/S0163-7258(01)00143-7
DO - 10.1016/S0163-7258(01)00143-7
M3 - Review article
C2 - 11707292
AN - SCOPUS:0035156083
SN - 0163-7258
VL - 91
SP - 1
EP - 34
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 1
ER -