Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular Ca 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) recently emerged as pivotal regulators of cellular senescence. However, how Ca levels are controlled during this process is barely known. Here, we report that intracellular Ca contents increase in response to many senescence inducers in immortalized human mammary epithelial cells (HMECs) and that expression of calbindin 1 (CALB1), a Ca-binding protein, is upregulated in this context, through the Ca-dependent calcineurin/NFAT pathway. We further show that overexpression of CALB1 buffers the rise in intracellular Ca levels observed in senescent cells. Finally, we suggest that increased expression of Ca-binding proteins calbindins is a frequent mark of senescent cells. This work thus supports that, together with Cachannels, Ca-binding proteins modulate Ca levels and flux during cellular senescence. This opens potential avenues of research to better understand the role of Ca and of Ca-binding proteins in regulating cellular senescence.