Alternative Isoforms as Molecular Modulators of Cellular Senescence in Cancer

Abstract

Simple Summary Cells exposed to damaging or stressful conditions can enter senescence, a stable state in which they stop dividing and undergo functional changes, including the production of secreted factors known as the senescence-associated secretory phenotype. Senescence can protect against tumor formation by preventing damaged cells from continuing to proliferate, but persistent senescent cells can also promote tumor progression in some contexts. Part of this variability may arise because cells can splice or start reading their genetic instructions differently, producing several versions, or isoforms, of the same protein. Most human genes produce such versions; of the nearly one thousand genes linked to senescence, only a handful have been studied. This review brings together how these versions influence whether cells enter, maintain, or escape senescence. Organizing the evidence by how directly each finding has been demonstrated clarifies what is established, what is speculative, and where the most promising research opportunities lie.