Epidermal growth factor receptor and Ink4a/Arf

Bachoo, Robert; Maher, Elizabeth A.; Ligon, Keith L.; Sharpless, Norman E.; Chan, Suzanne; You, M. James; Tang, Yi; DeFrances, Jessica; Stover, Elizabeth H.; Weissleder, Ralph; Rowitch, David H.; Louis, David N.; DePinho, Ronald A.

doi:10.1016/s1535-6108(02)00046-6

Cited by 590 publications

(224 citation statements)

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“…On the other hand, by interfering with MDM2 (mouse double minute 2)‐dependent degradation of p53, p14/p19 ARF controls p53/p21 WAF1 ‐induced G1 or G2 cell cycle arrest (Gil & Peters, 2006). Remarkably, using knockout mice models for this locus, it was possible to reveal that these senescence features could be associated with the terminal differentiation program in some specific cell types including keratinocytes (Paramio et al ., 2001; Bachoo et al ., 2002), chondrocytes (Philipot et al ., 2014), myofibers (Pajcini et al ., 2010), and also megakaryocytic cells (Muñoz‐Espín & Serrano, 2014). Megakaryocytic cells, myeloid‐derived immune cells from which blood platelets originate, are required for wound healing and immune responses (Besancenot et al ., 2010), opening new avenues to explore features of senescence in other types of immune cells.…”

Section: Cellular Senescence and Immune Cell Fate Decisionmentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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SummaryCellular senescence occurs not only in cultured fibroblasts, but also in undifferentiated and specialized cells from various tissues of all ages, in vitro and in vivo. Here, we review recent findings on the role of cellular senescence in immune cell fate decisions in macrophage polarization, natural killer cell phenotype, and following T‐lymphocyte activation. We also introduce the involvement of the onset of cellular senescence in some immune responses including T‐helper lymphocyte‐dependent tissue homeostatic functions and T‐regulatory cell‐dependent suppressive mechanisms. Altogether, these data propose that cellular senescence plays a wide‐reaching role as a homeostatic orchestrator.

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Section: Cellular Senescence and Immune Cell Fate Decisionmentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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“…A strategy to circumvent some of the limitations of xenotranplantation while preserving the flexibility of transplant tumor model may involve the injection of genetically modified mouse cells, including lineage‐restricted stem/progenitor cells, orthotopically into syngeneic, immunocompetent mice (Bachoo et al., 2002; Heyer et al., 2010). This “mouse‐in‐mouse” transplant model has the advantage over human xenotransplant models to expose tumor development to the same immunological barriers that are present in GEMMs of cancer, albeit without the genetic heterogeneity that distinguishes otherwise apparently similar human tumors.…”

Section: Harnessing Mouse Models Of Cancer To Investigate Individualimentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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It is a time of great promise and expectation for the applications of knowledge about mechanisms of cancer toward more effective and enduring therapies for human disease. Conceptualizations such as the hallmarks of cancer are providing an organizing principle with which to distill and rationalize the abject complexities of cancer phenotypes and genotypes across the spectrum of the human disease. A countervailing reality, however, involves the variable and often transitory responses to most mechanism‐based targeted therapies, returning full circle to the complexity, arguing that the unique biology and genetics of a patient's tumor will in the future necessarily need to be incorporated into the decisions about optimal treatment strategies, the frontier of personalized cancer medicine. This perspective highlights considerations, metrics, and methods that may prove instrumental in charting the landscape of evaluating individual tumors so to better inform diagnosis, prognosis, and therapy. Integral to the consideration is remarkable heterogeneity and variability, evidently embedded in cancer cells, but likely also in the cell types composing the supportive and interactive stroma of the tumor microenvironment (e.g., leukocytes and fibroblasts), whose diversity in form, regulation, function, and abundance may prove to rival that of the cancer cells themselves. By comprehensively interrogating both parenchyma and stroma of patients' cancers with a suite of parametric tools, the promise of mechanism‐based therapy may truly be realized.

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“…Experiments with mature brain astrocytes have shown that combined loss of the tumor suppressor genes p16 Ink4 and p19 Arf and constitutive activation of the EGF receptor caused a loss of differentiation. These cells regained neural stem cell properties and formed glioblastomas when injected into mouse brains (Bachoo et al, 2002). Cancer stem cells can thus be derived both from normal stem cells and from more differentiated cells that are reprogrammed to express the properties of stem cells.…”

Section: Epigenetic Control Of Differentiation In Cancer Stem Cellsmentioning

confidence: 99%