The Immortal Senescence.
Activation of oncogenic signaling paradoxically results in the permanent withdrawal from cell cycle and induction of senescence (oncogene-induced senescence (OIS)). OIS is a fail-safe mechanism used by the cells to prevent uncontrolled tumor growth, and, as such, it is considered as the first barrier against cancer. In order to progress, tumor cells thus need to first overcome the senescent phenotype. Despite the increasing attention gained by OIS in the past 20 years, this field is still rather young due to continuous emergence of novel pathways and processes involved in OIS. Among the many factors contributing to incomplete understanding of OIS are the lack of unequivocal markers for senescence and the complexity of the phenotypes revealed by senescent cells in vivo and in vitro. OIS has been shown to play major roles at both the cellular and organismal levels in biological processes ranging from embryonic development to barrier to cancer progression. Here we will briefly outline major advances in methodologies that are being utilized for induction, identification, and characterization of molecular processes in cells undergoing oncogene-induced senescence. The full description of such methodologies is provided in the corresponding chapters of the book.
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC L3-317, Elm & Carlton Streets, Buffalo, NY, 14263, USA.
Anna
A
Bianchi-Smiraglia
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC L3-317, Elm & Carlton Streets, Buffalo, NY, 14263, USA.
Brittany C
BC
Lipchick
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC L3-317, Elm & Carlton Streets, Buffalo, NY, 14263, USA. mikhail.nikiforov@roswellpark.org.
Mikhail A
MA
Nikiforov
D000818:Animals; D015415:Biomarkers; D016922:Cellular Senescence / Q000502:physiology*; D004198:Disease Susceptibility; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009857:Oncogenes; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D001616:beta-Galactosidase
Chromatin modifications; Hayflick limit; Oncogene-induced senescence; RAF; RAS; Senescence; Telomeres; p16INK4a; p21WAF1/CIP1; p53; β-galactosidase