Fig. 8
From: Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation
Working model of the “YB-1-PARP1” pathway involved in CDK4/6i resistance. CDK4/6i-resistant breast cancer cells display elevated PARP1 expression and YB-1 activation. CDK4/6i treatment may promote YB-1 phosphorylation at S102, and enhanced YB-1 phosphorylation leads to the binding of YB-1 to the promoter region of PARP1, which results in transcriptional activation of PARP1. Phosphorylated YB-1 can control cell cycle progression by strengthening PARP1-mediated DNA damage repair. Increasing PARP1 is crucial for promoting the cell cycle progression, which is the key role of PARP1 in removing the blocking effect of CDK4/6i on G1/S transformation of cells. The role of bypass activation of the cell cycle in PARP1 upregulation and YB-1 phosphorylation is crucial for CDK4/6i resistance