title: Nemo-like kinase (NLK) inhibits the progression of NSCLC via negatively modulating WNT signaling pathway.
abstract: Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, is a critical regulator of various cancers. NLK expression was evaluated by Western blot in 8 paired fresh non-small-cell lung cancer (NSCLC) tissues and immunohistochemistry (IHC) on 83 paraffin-embedded slices. NLK was lowly expressed in NSCLC and significantly associated with NSCLC histological differentiation, clinical stage, lymph node status, and Ki-67. Multivariate analysis indicated that low NLK expression was an independent prognostic factor for NSCLC patients' low survival rate. In vitro, after the release of NSCLC cell line A549 from serum starvation, the expression of NLK was downregulated, whereas the cell-cycle-related proteins were upregulated. In addition, we used RNA interference to knock down NLK expression, then observed its effects on NSCLC's growth in vitro. Western blot analyses indicated that deletion of NLK was positively correlated with cell-cycle-related proteins. The present investigation demonstrated that suppression of NLK expression resulted in significant promotion of proliferation in NSCLC cells. And flow cytometry further indicated that loss of NLK promoted cell proliferation by facilitating S-phase and mitotic entry. Besides, the transcription activity of β-catenin/TCF in A549 cells was remarkably enhanced when NLK was knocked down, which suggested that NLK participated in NSCLC cell proliferation via medulating Wnt signaling pathway. Based on these findings, we can provide a potential strategy for NSCLC therapy.
authors.affiliation: Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Lv
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wan
authors.forename: Buyou
authors.initials: B
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Yifei
authors.initials: Y
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Ni
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Cong
authors.forename: Guoxin
authors.initials: G
authors.lastname: Mao
authors.forename: Qun
authors.initials: Q
authors.lastname: Xue
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D051176:beta Catenin; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases
keywords: NLK; NON-SMALL-CELL LUNG CANCER; PROGNOSIS; PROLIFERATION; WNT