title: Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer.
abstract: It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC.
authors.affiliation: Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhen
authors.forename: Dongming
authors.initials: D
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Weimin
authors.initials: W
authors.lastname: Yao
authors.forename: Aibing
authors.initials: A
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Hongli
authors.initials: H
authors.lastname: Gu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Huang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Quanchao
authors.initials: Q
authors.lastname: Lyu
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; C530104:CCND1 protein, human; C114487:PDCD4 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4