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

Autor: Feng T; Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.; Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China., Xu X; Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.; Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, Shandong, China., Wang X; Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China., Tang W; Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China., Lu Y; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. luyi@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2024 Dec 18; Vol. 15 (12), pp. 889. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1038/s41419-024-07233-0
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All the participating subjects provided signed informed consent, and the experimental protocols were approved by the Ethics Committee of Shandong University (ECSBMSSDU2022-1-9). Consent for publication: All authors provided consent for publication.
(© 2024. The Author(s).)
Databáze: MEDLINE
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