title: Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression.
abstract: We aimed to investigate the clinical significance of the expression of novel scaffold protein CARMA3 in non-small-cell lung cancer (NSCLC) and the biological function of CARMA3 in NSCLC cell lines. We observed moderate to high CARMA3 staining in 68.8% of 141 NSCLC specimens compared to corresponding normal tissues. The overexpression of CARMA3 was significantly correlated with TNM stage (P = 0.022) and tumor status (P = 0.013). CARMA3 upregulation also correlated with a shorter survival rate of patients of nodal status N0 (P = 0.042)as well as the expression of epidermal growth factor receptor (EGFR) (P = 0.009). In EGFR mutation positive cases, CARMA3 expression was much higher (87.5%) compared to non-mutation cases (66.1%). In addition, we observed that knockdown of CARMA3 inhibits tumor cell proliferation and invasion, and induces cell cycle arrest at the boundary between the G1 and S phase. We further demonstrated a direct link between CARMA3 and NF-κB activation. The change of biological behavior in CARMA3 knockdown cells may be NF-κB-related. Our findings demonstrated, for the first time, that CARMA3 was overexpressed in NSCLC and correlated with lung cancer progression, EGFR expression, and EGFR mutation. CARMA3 could serve as a potential companion drug target, along with NF-kB and EGFR in EGFR-mutant lung cancers.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China.
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Li
authors.forename: Lianyue
authors.initials: L
authors.lastname: Qu
authors.forename: Qianze
authors.initials: Q
authors.lastname: Dong
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Wenting
authors.initials: W
authors.lastname: Luo
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
authors.forename: Xueshan
authors.initials: X
authors.lastname: Qiu
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000096:biosynthesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016196:S Phase / Q000235:genetics; D015996:Survival Rate
chemical_list: D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; D066246:ErbB Receptors