Rafting Down the Metastatic Cascade: The Role of Lipid Rafts in Cancer Metastasis, Cell Death, and Clinical Outcomes.

Lipid rafts are tightly packed, cholesterol- and sphingolipid-enriched microdomains within the plasma membrane that play important roles in many pathophysiologic processes. Rafts have been strongly implicated as master regulators of signal transduction in cancer, where raft compartmentalization can promote transmembrane receptor oligomerization, shield proteins from enzymatic degradation, and act as scaffolds to enhance intracellular signaling cascades. Cancer cells have been found to exploit these mechanisms to initiate oncogenic signaling and promote tumor progression. This review highlights the roles of lipid rafts within the metastatic cascade, specifically within tumor angiogenesis, cell adhesion, migration, epithelial-to-mesenchymal transition, and transendothelial migration. In addition, the interplay between lipid rafts and different modes of cancer cell death, including necrosis, apoptosis, and anoikis, will be described. The clinical role of lipid raft-specific proteins, caveolin and flotillin, in assessing patient prognosis and evaluating metastatic potential of various cancers will be presented. Collectively, elucidation of the complex roles of lipid rafts and raft components within the metastatic cascade may be instrumental for therapeutic discovery to curb prometastatic processes. ©2020 American Association for Cancer Research.