Acrylamide-mediated errors in the cell cycle regulation are associated with altered TORC2 signaling in Schizosaccharomyces pombe.

Acrylamide (AA) poses a significant risk to living organisms as it is linked to serious health concerns. AA exposure triggers oxidative stress in cells through elevated ROS and modulation of antioxidant enzymes activities and expression of genes encoding antioxidant enzymes. AA-induced cell proliferation defects are linked to affected cell cycle regulation demonstrated by changes in the expression of genes encoding the major cell cycle regulators cdc2, cdc13, and cdc25, Additionally, cell division defects can be linked to changes in the expression of ark1 and cdc15, and AA-induced errors in chromosome segregation. The stress response involves signaling pathways like MAPKs (Mitogen-activated protein kinases) or the target of rapamycin (TOR) constituting two complexes TORC 1 and 2. As TORC2 manages the cell response to various stresses, its involvement in AA-mediated stress has been demonstrated by changes in the expression of tor1, wat1, ste20, sin1, bit61 encoding TORC2 members, and gad8 encoding a direct Tor1substrate, Gad8. To our surprise, AA has not affected the expression of sty1, which encodes the major stress-regulating kinase of the MAPK pathway in S. pombe. In the presented study we demonstrate, for the first time, that exposure to AA disrupts cellular homeostasis by altering TORC2 signaling and cell cycle regulation ultimately leading to carcinogenesis.