title: C-Jun N-terminal kinase (JNK) mediates Wnt5a-induced cell motility dependent or independent of RhoA pathway in human dental papilla cells.
abstract: Wnt5a plays an essential role in tissue development by regulating cell migration, though the molecular mechanisms are still not fully understood. Our study investigated the pathways involved in Wnt5a-dependent cell motility during the formation of dentin and pulp. Over-expression of Wnt5a promoted cell adhesion and formation of focal adhesion complexes (FACs) in human dental papilla cells (hDPCs), while inhibiting cell migration. Instead of activating the canonical Wnt signal pathway in hDPCs, Wnt5a stimulation induced activation of the JNK signal in a RhoA-dependent or independent manner. Inhibiting JNK abrogated Wnt5a-induced FACs formation but not cytoskeletal rearrangement. Both dominant negative RhoA (RhoA T19N) and constitutively active RhoA mutants (RhoA Q63L) blocked the Wnt5a-dependent changes in hDPCs adhesion, migration and cytoskeletal rearrangement here too, with the exception of the formation of FACs. Taken together, our study suggested that RhoA and JNK signaling have roles in mediating Wnt5a-dependent adhesion and migration in hDPCs, and the Wnt5a/JNK pathway acts both dependently and independently of the RhoA pathway.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yingying
authors.initials: Y
authors.lastname: Su
authors.forename: Ruimin
authors.initials: R
authors.lastname: Li
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lin
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism; D003771:Dental Papilla / Q000166:cytology* / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D051419:Paxillin; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D048031:JNK Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein