FIGURE 1.

Cancer metastasis and TGF-β signaling. Cancer cells alter their morphology through epithelial-mesenchymal transition (EMT) induced by TGF-β signaling pathway activity, increasing their migratory potential. Invading the basement membrane and the extracellular matrix, tumor cells reach the vasculature (blood or lymph vessels) and become circulating tumor cells (CTCs) after intravasation. Gradually, the magnitudes of TGF-β signaling increase dramatically to enable the EMT-invasion processes. Cancer cells reach a secondary site after extravasation. Following TGF-β signaling reduction and consequent mesenchymal-epithelial transition (MET), cancer cells colonization proceeds to the growth of a metastatic lesion. Anti-TGF-β therapies administered in early stage cancers, before initial invasion, would inhibit metastasis by avoiding EMT. The same strategies used to treat late-stage cancers would also induce MET and seeding of secondary tumors.