Showing papers by "Darren J. Baker published in 2023"

Cellular senescence: beneficial, harmful, and highly complex

Abstract: The contribution of cellular senescence to a diverse range of biological processes, including normal physiology, ageing, and pathology were long overlooked but have now taken centre stage. In this Editorial, we will briefly outline the review and original work articles contained in The FEBS Journal's Special Issue on Senescence in Ageing and Disease. It is beginning to be appreciated that senescent cells can exert both beneficial and adverse effects following tissue injury. Additionally, while these cells play critical roles for maintaining a healthy physiology, they also promote ageing and certain pathological conditions (including developmental disorders). Progress has been made in re‐defining and identifying senescent cells, especially in slow‐proliferating or terminally differentiated tissues, such as the brain and cardiovascular system. Novel approaches and techniques for isolating senescent cells will greatly increase our appreciation for senescent properties in tissues. The inter‐organ communication between senescent cells and other residents of the tissue microenvironment, via the senescence‐associated secretory phenotype (SASP), is a focus of several reviews in this Special Issue. The importance of the SASP in promoting tumour development and the evolution of SARS CoV‐2 variants is also highlighted. In one of the two original articles included in the issue, the impact of dietary macronutrients and the presence of senescent cells in mice is investigated. Lastly, we continue to deepen our understanding on the use of senolytics and senomorphics to specifically target senescent cells or their secreted components, respectively, which is discussed in several of the reviews included here.

Hyperphosphorylated PTEN exerts oncogenic properties

Abstract: Abstract PTEN is a multifaceted tumor suppressor that is highly sensitive to alterations in expression or function. The PTEN C-tail domain, which is rich in phosphorylation sites, has been implicated in PTEN stability, localization, catalytic activity, and protein interactions, but its role in tumorigenesis remains unclear. To address this, we utilized several mouse strains with nonlethal C-tail mutations. Mice homozygous for a deletion that includes S370, S380, T382 and T383 contain low PTEN levels and hyperactive AKT but are not tumor prone. Analysis of mice containing nonphosphorylatable or phosphomimetic versions of S380, a residue hyperphosphorylated in human gastric cancers, reveal that PTEN stability and ability to inhibit PI3K-AKT depends on dynamic phosphorylation-dephosphorylation of this residue. While phosphomimetic S380 drives neoplastic growth in prostate by promoting nuclear accumulation of β-catenin, nonphosphorylatable S380 is not tumorigenic. These data suggest that C-tail hyperphosphorylation creates oncogenic PTEN and is a potential target for anti-cancer therapy.

Senescent cells as thermostats of antitumor immunity

Abstract: Harnessing the immunogenic potential of senescent cells may be a viable but context-dependent opportunity to boost antitumor immunity. Description Harnessing the immunogenic potential of senescent cells may be a viable but context-dependent opportunity to boost antitumor immunity.