title: PKCα-GSK3β-NF-κB signaling pathway and the possible involvement of TRIM21 in TRAIL-induced apoptosis.
abstract: Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a highly promising therapeutic agent for cancer treatment, owing to its ability to selectively target tumor cells for cell death while having little effect on most normal cells. However, recent research has found that many cancers, including non-small cell lung cancer (NSCLC), display resistance to TRAIL. Therefore, it is important to elucidate the molecular mechanisms governing the resistance of tumor cells to TRAIL treatment. In this study, we show that GSK3β antagonized TRAIL-induced apoptosis in H1299 NSCLC cells, and determined that the PKCα isozyme is an upstream regulator of GSK3β that phosphorylates and inactivates GSK3β, thereby sensitizing cancer cells to TRAIL-induced apoptosis. Furthermore, we demonstrated that the anti-apoptotic effect of GSK3β is mediated by the NF-κB pathway, whereas the tripartite motif 21 (TRIM21) was able to inhibit the activation of NF-κB by GSK3β, and leads to the promotion of cell apoptosis. Taken together, our study further delineated the underpinning mechanism of resistance to TRAIL-induced apoptosis in H1299 cells, and provided new clues for sensitizing NSCLC cells to TRAIL therapy.
authors.affiliation: a Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Gao
authors.affiliation: a Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Xu
authors.affiliation: b Institute of Orthopedic Diseases and Department of Orthopedics, the First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
authors.forename: Huan-Tian
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: c Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
authors.forename: Miaojuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Wensi
authors.initials: W
authors.lastname: Huang
authors.affiliation: d Institute of Biomedicine, and National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, China.
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: a Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Langxia
authors.initials: L
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism* / Q000494:pharmacology; D000099207:SS-A Antigen
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; D016328:NF-kappa B; D051571:Protein Kinase C-alpha; D012261:Ribonucleoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099207:SS-A Antigen; C000605506:GSK3B protein, human
keywords: GSK3β; H1299 cells; PKCα; TRAIL; TRIM21; cellules H1299