How Do Cancer Cells Acquire the Fuel Needed to Support Cell Growth?

Abstract

In this paper we consider whether the dependency of metazoan cells on extracellular signals to maintain cell survival resultsin an important barrier that must be overcome during carcinogenesis. It is now generally accepted that a major barrier to cancercomes from the inability of cells to enter and progress through the cell cycle in a cell-autonomous fashion. Most of theoncogenes studied over the last two decades contribute to the ability of the cancer cell to enter and progress through the cellcycle in the absence of the instructional signals normally imparted by extracellular growth factors. Over the last two decades,it has begun to be appreciated that there is a second potential barrier to transformation. It appears that all cells in multicellularorganisms need extracellular signals not only to initiate proliferation, but also to maintain cell survival. Every cell in ourbody expresses the proteins necessary to execute its own death by apoptosis. A cell will activate this apoptotic program bydefault unless it receives signals from the extracellular environment that allow the cell to suppress the apoptotic machineryit expresses. It now appears that the molecular basis of this suppression lies in the signaling pathways that regulate cellularnutrient uptake and direct the metabolic fate of those nutrients.