Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular Ca 2+ Levels in Senescent Cells.

In response to many stresses, such as oncogene activation or DNA damage, cells can enter cellular senescence, a state of proliferation arrest accompanied by a senescence-associated secretory phenotype (SASP). Cellular senescence plays a key role in many physiopathological contexts, including cancer, aging and aging-associated diseases, therefore, it is critical to understand how senescence is regulated. Calcium ions (Ca 2+ ) recently emerged as pivotal regulators of cellular senescence. However, how Ca 2+ levels are controlled during this process is barely known. Here, we report that intracellular Ca 2+ contents increase in response to many senescence inducers in immortalized human mammary epithelial cells (HMECs) and that expression of calbindin 1 (CALB1), a Ca 2+ -binding protein, is upregulated in this context, through the Ca 2+ -dependent calcineurin/NFAT pathway. We further show that overexpression of CALB1 buffers the rise in intracellular Ca 2+ levels observed in senescent cells. Finally, we suggest that increased expression of Ca 2+ -binding proteins calbindins is a frequent mark of senescent cells. This work thus supports that, together with Ca 2+ channels, Ca 2+ -binding proteins modulate Ca 2+ levels and flux during cellular senescence. This opens potential avenues of research to better understand the role of Ca 2+ and of Ca 2+ -binding proteins in regulating cellular senescence.