Figure 1.

Major signaling pathways in chemoresistance and PDK1 implication. PDK1 is implicated in a number of signaling pathways and cancers. Complex formation with COL11A1 results in PDK1 stabilization and resistance to ubiquitin (Ub)-proteasome pathway degradation in epithelial ovarian carcinoma, its instigation by sfRON leads to EMT in high-grade serous ovarian cancer, whereas PDK1 inhibition combined with CAMKK2 inhibition leads to reduction of phospho-Akt levels and decreased platinum resistance in ovarian cancer. Sensitization of breast cancer cells to drugs such as tamoxifen and paclitaxel is correlated with the effect and sustaining of PI3K and ER signaling through SGK1/3 and Foxo1/3 isoforms, where components such as PPARβ/δ have a stimulating effect, and PDK1 inhibitors such as 2-O-Bn-InsP₅ and OSU-03012 have proven to be effective. In other types of cancer, proteins such as MTDH and TCRP1 are shown to directly or indirectly activate PDK1, and the tumour suppressor TUSC4 is shown to form a complex with it and negatively regulate the signaling cascade.