title: Tumor cell dormancy induced by p38SAPK and ER-stress signaling: an adaptive advantage for metastatic cells?
abstract: The mechanisms that determine whether a tumor cell that has disseminated to a secondary site will resume growth immediately, die or enter a state of dormancy are poorly understood. Although tumor dormancy represents a common clinical finding, studying the mechanisms behind this stage of tumor progression has been challenging. Furthermore, it is thought that dormant tumor cells are refractory to chemotherapy due to their lack of proliferation. However, whether this is the only reason for their chemo-resistance remains to be proven. In this review we summarize recent findings that provide a mechanistic explanation about how stress signaling through the p38(SAPK) pathway and ER-stress signaling may coordinate the induction of growth arrest and drug-resistance in a model of squamous carcinoma dormancy. We further discuss how dormant tumor cells may enter this stage to adapt to strenuous conditions that do not favor immediate growth after dissemination. Finally, we propose that this response may recapitulate an evolutionarily conserved program of life-span extension through adaptation and tolerance to stress.
authors.affiliation: Department of Biomedical Sciences, School of Public Health and Center for Excellence in Cancer Genomics, University at Albany, State University of New York, Rensselaer, NY 12144-3456, USA.
authors.forename: Aparna C
authors.initials: AC
authors.lastname: Ranganathan
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Adam
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Julio A
authors.initials: JA
authors.lastname: Aguirre-Ghiso
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D015852:Eukaryotic Initiation Factor-2 / Q000819:agonists; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015398:Signal Transduction; D019892:eIF-2 Kinase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D019892:eIF-2 Kinase; D048051:p38 Mitogen-Activated Protein Kinases