Roles of anoikis in hepatocellular carcinoma therapy and the assessment of anoikis-regulatory molecules as therapeutic targets.

As the fourth leading cause of death from cancer and the sixth most common neoplasm in the world, hepatocellular carcinoma (HCC) is responsible for ninety percent of all primary liver cancers. There are four mechanisms that contribute to the spread of cancer: the separation of cells from the primary neoplasm, their survivability during metastasis, extravasation, and the development of secondary tumors at remote locations. In addition to its role in the development of a scaffold for cell adhesion, the extracellular matrix (ECM) also plays a role in the stimulation of signal transduction and the regulation of essential cellular mechanisms, including proliferation, migration, differentiation, and viability. The disruption of cell-ECM interactions and the ensuing separation of cells from the primary ECM trigger anoikis, a form of programmed cell death. One of the most effective factors in suppressing anoikis is ECM receptors from the integrin family. Cell migration, proliferation, and survival are primarily governed by the formation of physical connections with the cytoskeleton and the conveyance of signals between cells and the ECM via integrin receptors.