How do cancer cells acquire the fuel needed to support cell growth?
In this paper we consider whether the dependency of metazoan cells on extracellular signals to maintain cell survival results in an important barrier that must be overcome during carcinogenesis. It is now generally accepted that a major barrier to cancer comes from the inability of cells to enter and progress through the cell cycle in a cell-autonomous fashion. Most of the oncogenes studied over the last two decades contribute to the ability of the cancer cell to enter and progress through the cell cycle 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 multicellular organisms need extracellular signals not only to initiate proliferation, but also to maintain cell survival. Every cell in our body expresses the proteins necessary to execute its own death by apoptosis. A cell will activate this apoptotic program by default unless it receives signals from the extracellular environment that allow the cell to suppress the apoptotic machinery it expresses. It now appears that the molecular basis of this suppression lies in the signaling pathways that regulate cellular nutrient uptake and direct the metabolic fate of those nutrients.
Thompson
C B
CB
Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, 19104, USA.
Bauer
D E
DE
Lum
J J
JJ
Hatzivassiliou
G
G
Zong
W-X
WX
Zhao
F
F
Ditsworth
D
D
Buzzai
M
M
Lindsten
T
T
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D049109:Cell Proliferation; D002470:Cell Survival; D005947:Glucose / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
D006133:Growth Substances; D008055:Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; D000255:Adenosine Triphosphate; D005947:Glucose