Fig. 9.

Schematic illustration of signal transduction pathways involved in metastasis cascade. If normal epithelial cells (orange) detach from the membrane, it undergoes apoptosis, known as anoikis (brown), while the tumor cells (red) resist apoptosis through the activation of anti-apoptotic pathways such as PI3-AKT, MAPK (anti-apoptotic pathways). With the loss of E-cadherin receptors (promoted by TGF-β pathway), the tumor cells undergo a transition from non-mobile (epithelial) to mobile (mesenchymal) form (red tumor cell with a tail). These mobile or transformed tumor cells intravasate into blood vessels and transported to a new site, where they extravasate and localize (brain shown in blue). At the new site, tumor cells proliferate through the activation of Wnt, Notch, Hedgehog, and other related pathways to develop a new tumor (metastasis). New blood vessels are formed (angiogenesis) by synthesizing angiogenic factors by Nf- kappa B and other signaling pathways. The new blood vessels are employed for the tumor cells' nutrition and transport (intravasation and extravasation). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)