Oncogenic senescence: a multi-functional perspective

نویسندگان

  • Darren J. Baker
  • Fatouma Alimirah
  • Jan M. van Deursen
  • Judith Campisi
  • Jeffrey Hildesheim
چکیده

Cellular senescence is defined as an irreversible growth arrest with the acquisition of a distinctive secretome. The growth arrest is a potent anticancer mechanism whereas the secretome facilitates wound healing, tissue repair, and development. The senescence response has also become increasingly recognized as an important contributor to aging and age-related diseases, including cancer. Although oncogenic mutations are capable of inducing a beneficial senescence response that prevents the growth of premalignant cells and promotes cancer immune-surveillance, the secretome of senescent cells also includes factors with pro-tumorigenic properties. On June 23rd and 24th, 2016, the Division of Cancer Biology of the National Cancer Institute sponsored a workshop to discuss the complex role of cellular senescence in tumorigenesis with the goal to define the major challenges and opportunities within this important field of cancer research. Additionally, it was noted how the development of novel tools and technologies are required to accelerate research into a mechanistic understanding of senescent cells in carcinogenesis in order to overcome the current limitations in this exciting, yet ill-defined area.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models.

KRAS is one of the most frequently mutated human oncogenes. In some settings, oncogenic KRAS can trigger cellular senescence, whereas in others it produces hyperproliferation. Elucidating the mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches in RAS-driven cancers. Using a combination of functional genomics and mouse genetics, we identif...

متن کامل

Caspase-2 regulates oncogene-induced senescence

Cellular senescence is activated by numerous cellular insults, in particular those driving cancer formation, resulting in stable proliferation arrest and acquisition of specific features. By self-opposing to oncogenic stimulation, senescence is considered as a failsafe program, allowing, when functional, to inhibit cancers occurrence. Compelling evidences suggest a tumor suppressive activity of...

متن کامل

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and mal...

متن کامل

Oncogenic ras and p53 cooperate to induce cellular senescence.

Oncogenic activation of the mitogen-activated protein (MAP) kinase cascade in murine fibroblasts initiates a senescence-like cell cycle arrest that depends on the ARF/p53 tumor suppressor pathway. To investigate whether p53 is sufficient to induce senescence, we introduced a conditional murine p53 allele (p53(val135)) into p53-null mouse embryonic fibroblasts and examined cell proliferation and...

متن کامل

Molecular genetic control of leaf lifespan in plants - A review

Leaf senescence constitutes the last stage of leaf development in plants and proceeds through a highly regulated program in order to redistribution of micro- and macro-nutrients from the senescing leaves to the developing/growing plant organs. Initiation and progression of leaf senescence is accompanied by massive sequential alterations at various levels of leaf biology including leaf morpholog...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017