Opposing roles of mitogenic and stress signaling pathways in the induction of cancer dormancy.
Cancer dormancy is a poorly understood stage of cancer progression. However, the ability to control this step of the disease offers novel therapeutic opportunities. Here we summarize recent findings that implicate the extracellular matrix and adhesion receptor signaling in the escape or induction of tumor dormancy. We further review evidence suggesting that imbalances in the activity ratio of ERK to p38 signaling may determine the fate (i.e., tumorigenicity vs. dormancy) of different carcinoma cells. Special attention is placed on the mechanisms that p38 signaling regulates during the induction of dormancy and how modulation of these pathways may offer a therapeutic opportunity. We also review evidence for a novel drug-resistance mechanism in dormant tumor cells that when blocked may enable killing of dormant tumor cells. Finally, we explore the notion that dormancy of tumor cells may be the result of a selective adaptive response that allows disseminated tumor cells to pause their growth and cope with stress signaling imposed by dissemination and/or treatment until growth can be restored.
Ranganathan
Aparna C
AC
Department of Biomedical Sciences, School of Public Health and Center for Excellence in Cancer Genomics, University at Albany, New York, USA.
Adam
Alejandro P
AP
Aguirre-Ghiso
Julio A
JA
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D023421:Models, Animal; D009362:Neoplasm Metastasis; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013312:Stress, Physiological / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D039081:Integrin alpha5beta1; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases