PGRN protects against serum deprivation-induced cell death by promoting the ROS scavenger system in cervical cancer

Abstract Progranulin (PGRN), 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 (ROS) 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 (SOD), 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 (NFE2L2)-antioxidant response element (ARE) 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.