Journal
BIOCHEMISTRY AND CELL BIOLOGY
Volume -, Issue -, Pages -Publisher
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/bcb-2022-0361
Keywords
ferroptosis; ovarian cancer; chemoresistance; AKT1; autophagy; FTH1
Categories
Ask authors/readers for more resources
Resistance to cisplatin-based chemotherapy is a major obstacle in treating ovarian cancer, but chemotherapy-resistant tumor cells may have vulnerability to other cell death pathways. Our study found that cisplatin-resistant ovarian cancer cells are more susceptible to erastin-induced ferroptosis, which is not due to the weakening of classical ferroptosis defense proteins but the reduction of ferritin heavy chain (FTH1). These resistant cells maintain high levels of autophagy to evade chemotherapy, leading to increased autophagic degradation of FTH1. Loss of AKT1 was identified as the reason for the elevated autophagy level in cisplatin-resistant ovarian cancer cells. Our findings provide new insights into reversing cisplatin resistance by targeting the ferroptosis pathway, with AKT1 potentially serving as a molecular marker for susceptibility to ferroptosis.
Resistance to cisplatin (DDP)-based chemotherapy is an important reason for the failure of ovarian cancer treatment. How-ever, tumor cells resistant to chemotherapy may expose vulnerability to other cell death pathways. Here, we found that DDP-resistant ovarian cancer cells are more susceptible to erastin-induced ferroptosis. It should be noted that this vulnerability does not depend on the weakening of classical ferroptosis defense proteins, but is caused by the reduction of ferritin heavy chain (FTH1). DDP-resistant ovarian cancer cells maintain a high level of autophagy to escape the pressure of chemotherapy, which ultimately leads to increased autophagic degradation of FTH1. We further revealed that the loss of AKT1 was the reason for the increased autophagy level of DDP-resistant ovarian cancer cells. Our study provides new insights into reversing DDP resistance in ovarian cancer by targeting ferroptosis pathway, and AKT1 may be a molecular marker of susceptibility to ferroptosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available