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M. Jiang
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-083 - DKK1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via β-Catenin Signaling Pathway (ID 7369)
09:30 - 09:30 | Author(s): M. Jiang
- Abstract
Background:
Non-small cell lung cancer(NSCLC) accounts for 80–85% of all lung cancers, the leading cause of cancer-related deaths worldwide .NSCLC progression and metastasis have been the primary causes for poor clinical outcomes of patients. Therefore, it is essential to explore the underlying molecular mechanisms of NSCLC migration and invasion; also, a diagnostic marker for NSCLC is an indispensable prerequisite.
Method:
DKK1 was knocked out by the lentivirus-mediated short hairpin RNA interference (shRNA) approach in H1299 and 95C NSCLC cell lines. Subsequently, the migration and invasion ability were assessed by wound healing and transwell assays. In addition, epithelial-mesenchymal transition (EMT) markers and β-catenin were examined by Western blot. The signaling pathway downstream of DKK1 was characterized using the Wnt signaling pathway inhibitor, IWP2, and GSK3β inhibitor, LiCl. Immunofluorescence analysis investigated the subcellular localization of β-catenin.
Result:
Knockdown of DKK1 caused reduced migration and invasion ability of H1299 and 95C cells. DKK1 silencing resulted in the downregulation of EMT-related proteins, such as Snail, ZEB1(zinc finger E-box binding homeobox 1), Besides, DKK1 silencing inhibitedβ-catenin and promoted the phosphorylation of β-catenin. Mechanism results indicated that the expression of β-catenin was reduced in H1299 or 95C cells after being treated with Wnt signaling inhibitor, IWP2. In addition, the inhibition of β-catenin phosphorylation by GSK3β inhibitor, LiCl, significantly enhanced the migration and invasion capacities in DKK1-KD cell lines. Furthermore, cell immunofluorescence revealed that nuclear β-catenin was reduced when DKK1 was knocked down.
Conclusion:
Taken together, these suggest that DKK1 induces the occurrence of EMT and promotes migration and invasion in NSCLC cells. Mechanically, β-catenin plays a vital role in DKK1-induced NSCLC cell migration and invasion, and DKK1 inhibits the phosphorylation of β-catenin, resulting in the increased nuclear localization of β-catenin.
