Affiliations 1 Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. 2 Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China. 3 Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, Shandong, China. 4 Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. luyi@sdu.edu.cn.
刊名
Cell death & disease
年份
2024
卷号
Vol.15 No.12
页码
889
ISSN
2041-4889
摘要
Progranulin , an autocrine growth factor with tumorigenic roles in a variety of tumors, is a putative survival factor for normal and cancer cells in vitro. However, the fundamental mechanism of PGRN-mediated survival of cancer cells suffering from various types of microenvironmental stresses, such as serum deprivation, remains unknown. We show here that serum deprivation decreases intracellular PGRN protein levels in cervical cancer cells. PGRN protects cervical cancer cells against serum depriv...更多
Progranulin , an autocrine growth factor with tumorigenic roles in a variety of tumors, is a putative survival factor for normal and cancer cells in vitro. However, the fundamental mechanism of PGRN-mediated survival of cancer cells suffering from various types of microenvironmental stresses, such as serum deprivation, remains unknown. We show here that serum deprivation decreases intracellular PGRN protein levels in cervical cancer cells. PGRN protects cervical cancer cells against serum deprivation-induced apoptosis, limits reactive oxygen species levels, maintains mitochondria integrity, and reduces oxidative damage of protein, lipid and DNA. PGRN enhances the ROS scavenger system, as evidenced by increased superoxide dismutase , catalase protein expression and activity, elevated GSH and NADPH levels and increased phase II detoxification enzyme expression in cervical cancer cells after serum withdrawal. The role of PGRN in ROS clearance is mediated by the PGRN-stimulated nuclear factor erythroid-derived 2-like 2 -antioxidant response element pathway. Our study reveals an antioxidant role of PGRN in supporting the survival of cervical cancer cells under oxidative stress. This insight provides a new perspective on the how cervical cancer cells adapt to microenvironmental stress, contributing to cell viability and other malignant characteristics.收起
