INVESTIGATING ZEB-1 MEDIATED DRUG RESISTANCE IN SOLID TUMORS

Abstract

The epithelial-to-mesenchymal transition (EMT) is a cellular program, through which epithelial cells lose their normal, epithelial phenotype, and become mesenchymal. This process is found to play a critical role in enhanced therapy resistance and metastatic capacities in many solid tumors. One of the most important players that activate EMT is Zeb1, which belongs to the family of ZEB transcription factors, and it alone was shown to affect the poor clinical outcomes of cancer patients due to elevating the radio-resistance and multidrug resistance in a variety of tumors. Here, we examined the effect of a combination of active compounds that are FDA approved drugs and inhibitors targeting protein kinase C (PKC) on the Zeb1 expressing breast cancer cells at distinct stages of the EMT, and concluded that the resistance of Zeb1 can be affected by kinase inhibitors, by counteracting its effect on cell cycle arrest at G1 proliferation phase. These results open new opportunities for manipulating the Zeb1-mediated therapy-resistance pathway in breast cancer, and consequently other solid tumors.