title: Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3.
abstract: Metastasis is the leading cause of death in lung cancer. Understanding the mechanisms underlying the process of metastasis is crucial for identifying novel anti-metastatic therapies. Studies indicate that the highly conserved developmental pathways, such as the Wnt and Notch signaling pathways, play important roles in the non-small cell lung cancer (NSCLC) tumorigenesis. However, the roles of both pathways in NSCLC metastasis are unclear. The present study aimed to investigate whether Wnt3a and Notch3, key components of the Wnt and Notch signaling pathways, respectively, regulate the metastatic abilities of NSCLC cells and whether there is some relationship during these regulatory events. Here, we observed that Wnt3a treatment upregulated, not only the protein expression of Notch3, but also the mRNA expression of Notch3 and its downstream genes, HES1 and HEYL. In addition, Wnt3a promoted cell invasion and anchorage-independent growth. Meanwhile, Wnt3a treatment caused epithelial‑mesenchymal transition (EMT)-like morphological changes and F-actin reorganization. The western blotting data showed that Wnt3a treatment decreased the expression of E-cadherin and increased the expression of N-cadherin and vimentin. Compared with Wnt3a treatment, Notch3 shRNA transfection had opposite effects. Furthermore, Notch3 shRNA weakened the effects of Wnt3a treatment on the in vitro cell invasion and EMT. Overall, these observations suggest that Wnt3a and Notch3 may promote the metastasis of NSCLC and Notch3 upregulation is required for the Wnt3a mediated increased metastatic abilities of NSCLC.
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biotechnology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Gongru
authors.initials: G
authors.lastname: Song
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zeshi
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000199:Actins / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D000072056:Transcription Factor HES-1; D015533:Transcriptional Activation; D015854:Up-Regulation; D014746:Vimentin / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000235:genetics; D060509:Wnt3A Protein / Q000235:genetics*
chemical_list: D000199:Actins; D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014746:Vimentin; D060509:Wnt3A Protein; C497364:HEYL protein, human; C499374:NOTCH3 protein, human; C555510:WNT3A protein, human; C078493:HES1 protein, human