Fig. 6: Aneuploidy-induced DNA damage results in the upregulation of the CRAF/MEK/ERK pathway.
From: Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage
A summary illustration of the study. When cells become aneuploid following chromosome mis-segregation, they acquire DNA damage that activates the DNA damage response (DDR). When p53 is intact, this results in p53 pathway activation. The increased basal levels of DDR render the cells more resistant to further induction of DNA damage. In parallel, acquisition of DNA damage activates the CRAF/MEK/ERK pathway, which fuels the DNA damage response. Consequently, aneuploid cells are more dependent than their diploid counterparts on CRAF, MEK, and ERK activity. Pharmacological induction of DNA damage further increases both the DNA damage response and the activation of CRAF/MEK/ERK pathway, and pharmacological inhibition of the CRAF/MEK/ERK pathway can thus sensitize aneuploid cells to DNA damage-inducing chemotherapies. The figure was created with BioRender.com.
