KLF6 tumor suppressor activity is associated to the induction of cellular senescence

SABATINO, ME; CARBAJOSA, S; PANSA, MF; BOCCO JL; VILLAFAÑEZ, F; GARCIA, AI; SORIA, G

Paris

Conferencia; International Cell Senescence Association (ICSA) Conference; 2017

ICSA

Krüppel-like factor 6 (KLF6) is a transcription factor involved in cell-cycle regulation and cellular differentiation. Indeed, KLF6 is considered a tumor suppressor whose expression is frequently lost in various human cancer types. In previous work, we shown that KLF6 knockdown in normal fibroblast led to cell transformation. As cellular senescence is a crucial anticancer mechanism that prevents growth of cells at risk for neoplastic transformation, we aimed to elucidate the impact of KLF6 on cellular senescence. This cellular process could be elicited through several mechanisms including oncogene activation, DNA damage and oxidative stress. Through H2O2-treatment we induced NIH3T3 fibroblast cells to become senescent, detected by senescence-associated beta galactosidase activity and heterochromatin foci (SAHF) formation. Then, stable transduction of shRNA for downregulation of KLF6 expression led to a decreased of the senescent cells index together with chromatin instability signs, thereby bypassing H2O2-induced cellular senescence. In addition, ectopic expression of KLF6 in HeLa cervical carcinoma cells was able to induce cellular senescence. This surprising finding, along with its cytostatic function upon oncogenic activation, suggests that KLF6 tumor suppressor activity could be mediated by cellular senescence as an alarm signal in response to certain stimuli that produce exacerbated proliferation or cell transformation.