A nanomechanical strategy involving focal adhesion kinase for overcoming drug resistance in breast cancer

Despite implementation of nanomechanical studies in cancer research, studies on the nanomechanical aspects of drug resistance in cancer are lacking. Here, we established the mechanical signatures of drug-resistant breast cancer cells using atomic force microscopy-based indentation techniques and functionalized nanopatterned substrates (NPS). Additionally, we examined the expression of proteins pertinent to focal adhesions in order to elucidate the molecular signatures responsible for the acquisition of drug resistance in breast cancer cells. Drug resistant breast cancer cells exhibited mechanical reinforcement, increased actin stress fibers, dysfunctional mechano-reciprocal interaction with the NPS, vinculin overexpression, and improved focal adhesion kinase (FAK) activity. Owing to differences in FAK activation upon co treatment with a FAK inhibitor, the drug-resistant breast cancer cells were eradicated more efficiently than invasive breast cancer cells having pro-survival activity. These findings demonstrated the potential of a novel co-treatment regimen using FAK inhibitors for overcoming drug resistance in breast cancer cells.(c) 2022 Elsevier Inc. All rights reserved.