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• W2022896763 abstract "Background: Invasive growth of epithelial tumor cells, a major cause of death from cancer in humans, involves loss of epithelial polarity and dedifferentiation. Transforming growth factor β (TGFβ) is regarded as a major tumor suppressor during early tumor development because it inhibits cell-cycle progression and tumor growth. Many dedifferentiated, late-stage tumors are resistant to growth inhibition by TGFβ, however, and even secrete TGFβ. In line with this, TGFβ is involved in angiogenesis, wound healing and epithelial–mesenchymal transition (EMT) during development. Ha-Ras-transformed mammary epithelial cells (EpRas) undergo TGFβ-induced EMT maintained via a TGFβ autocrine loop. Thus, we have analyzed whether signal transduction by the TGFβ receptor (TGFβR) is required for local tumor cell invasion and metastasis.Results: A dominant-negative type II TGFβR (TGFβRII-dn) was expressed using retroviral vectors in EpRas cells and highly metastatic mesenchymal mouse colon carcinoma cells (CT26). In both cell types, TGFβRII-dn blocked TGFβR signaling and heavily delayed tumor formation. In EpRas cells, TGFβRII-dn prevented EMT. In the dedifferentiated mesenchymal CT26 cells, TGFβRII-dn caused mesenchymal-to-epithelial transition and inhibited their in vitro invasiveness in several assays. In addition, TGFβRII-dn completely abolished metastasis formation by CT26 cells. Furthermore, several human carcinoma lines lost in vitro invasiveness when treated with neutralizing TGFβ antibodies or soluble receptor variants. Finally, human colon carcinoma cells (hnPCC) expressing a mutated, non-functional TGFβRII were non-invasive in vitro, a defect restored by re-expressing wild-type TGFβRII.Conclusions: Cell-autonomous TGFβ signaling is required for both induction and maintenance of in vitro invasiveness and metastasis during late-stage tumorigenesis. TGFβRII therefore represents a potential target for therapeutical intervention in human tumorigenesis." @default.
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• W2022896763 date "1998-11-01" @default.
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• W2022896763 title "TGFβ signaling is necessary for carcinoma cell invasiveness and metastasis" @default.
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• W2022896763 doi "https://doi.org/10.1016/s0960-9822(07)00533-7" @default.
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