Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

• DOI: 10.3390/ijms22010355
• Publication Date: 2020-12-31T15:10:37Z
• Authors: Cho-Yi Chen; Masaoki Kawasumi; Tien-Yun Lan; Chi-Lam Poon; Yi-Sian Lin; Pin-Jou Wu; Yao-Chung Chen; Bing-Hong Chen; Cheng-Hsien Wu; Jeng-Fan Lo; Rueyhung Roc Weng; Yi-Chen Sun; Kai-Feng Hung
• Keywords: Cellular adaptation

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked ER response; however, most evidence come from studies correlate expression markers poor prognosis or demonstrate proapoptosis by knockdown stress-responsive genes. Since in cancers usually persists essentially not induced genetic manipulations, we used low doses inducers at levels allowed cell adaptation occur order investigate effect on chemoresistance. We found prolonged tolerable promotes mesenchymal–epithelial transition, slows cell-cycle progression, delays S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased stress-adapted cells, implying their acquisition cisplatin Molecularly, proliferating nuclear antigen (PCNA) ubiquitination polymerase η, main responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated stress-adaptive enhanced resistance abrogated knockout η. also a fraction p53 cells translocated nucleus, these exhibited significant decline level damage. Consistently, showed coincided strong positivity glucose-related protein 78 (GRP78) immunostaining clinical biopsies, cisplatin-based chemotherapy less effective patients high stress. Taken together, this study uncovers enhances DNA repair damage tolerance, stressed gain chemotherapeutics.