Research Paper Volume 12, Issue 11 pp 10194—10210

Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prostate cancer cell lines

Figure 1. Effects of collagen, chemotherapeutic drugs on ROS, TP53, DDR1 and downstream signaling pathways on proliferation, drug resistance and aging. One signaling protein involved in regulating the Raf/MEK/ERK and PI3K/Akt pathways is DDR1. A ligand for DDR1 is collagen. Collagen is involved in the regulation of aging and in some cases tumorigenesis. Chemotherapeutic drugs and ROS can affect multiple signaling pathways and transcription factors such as TP53 and NF-κB which can alter the expression of proteins involved in cell growth, drug resistance and aging. ROS can induce various other signaling pathways such as Raf/MEK/ERK and PI3K/Akt which have effects on proliferation. Drug resistant cells often have altered levels of ROS. Some drug resistant cells display altered expression of drug transporters, signaling or apoptotic proteins. Treatment of cell lines with chemotherapeutic drugs frequently leads to the development of drug resistance by various mechanisms. Interactions between WT-TP53 and DDR1 and downstream Raf/MEK/ERK and PI3K/Akt pathways may have important consequences on cancer progression, drug resistance and aging.