PPP2CA Inhibition Promotes Ferroptosis Sensitivity Through AMPK/SCD1 Pathway in Colorectal Cancer.

Autor: Liang X; Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China., Zhang H; Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China., Shang W; Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China., Wang M; Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China., Li J; Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China., Zhao Y; Department of General Surgery, The Affiliated Jinling Hospital of Nanjing Medical University, 305 East Zhongshan Road, Nanjing, 210002, China., Fang C; Central Laboratory, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China. fangchao@njmu.edu.cn.
Jazyk: angličtina
Zdroj: Digestive diseases and sciences [Dig Dis Sci] 2024 Jun; Vol. 69 (6), pp. 2083-2095. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1007/s10620-024-08416-7
Abstrakt: Purpose: Colorectal cancer (CRC) is a very common malignancy of the digestive system. Despite a variety of treatments including surgery, chemotherapeutic and targeted drugs, the prognosis for patients with CRC is still unsatisfactory and the mortality remains high. Protein phosphorylation plays an essential role in tumorigenesis and progression and is also crucial for protein to act with proper functions. Ferroptosis is found widely involved in various diseases especially tumors as a newly identified programmed cell death.
Methods: In our study, we aimed at PPP2CA as a prospective target which may play a crucial role in CRC progression. In one hand, knockdown of PPP2CA significantly enhanced the malignant phenotype in HCT116. In the other hand, knockdown of PPP2CA significantly enhanced Erastin-induced ferroptosis as well.
Results: Specifically, knockdown of PPP2CA in HCT116 significantly increased the relative level of malondialdehyde (MDA), reactive oxygen species (ROS) and Fe 2+ , and decreased GSH/GSSG ratio after the treatment of certain concentration of Erastin. Besides, we found that the inhibition of PPP2CA further led to the suppression of SCD1 expression in CRC cells in a AMPK-dependent way.
Conclusion: Ultimately, we conclude that PPP2CA may regulate Erastin-induced ferroptosis through AMPK/SCD1 signaling pathway.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: