The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis

Figure 6

The dual role of TGFβ in human cancer. In summary, TGFβ acts as a tumor suppressor in normal cells and early carcinomas, while it promotes tumor metastasis in more advance stages of cancer. The tumor suppressive effects of TGFβ include cell cycle arrest, apoptosis and prevention of cell immortalization. TGFβ also induces EMT, marked by a decrease in cell-cell and cell-substrate contact, a reorganization of the actin cytoskeleton, as well as an increase in metalloproteinase synthesis and secretion. In human cancers, inactivating mutations in the TGFβ signaling components or activating mutations in oncogenic signaling pathways are often observed and provide an underlying basis for tumor development. These mutations attenuate the TGFβ tumor suppressive effects but do not affect its tumor promoting effects on cancer cells and on the surrounding environment, including EMT, cell migration and invasion, angiogenesis, immunosuppression, myofibroblast generation, chemoattraction, and tumor metastasis, further promoting TGFβ-induced tumor progression to secondary distant sites.