title: Neural cell adhesion molecule potentiates the growth of murine melanoma via β-catenin signaling by association with fibroblast growth factor receptor and glycogen synthase kinase-3β.
abstract: The neural cell adhesion molecule (NCAM) was recently shown to be involved in the progression of various tumors with diverse effects. We previously demonstrated that NCAM potentiates the cellular invasion and metastasis of melanoma. Here we further report that the growth of melanoma is obviously retarded when the expression of NCAM is silenced. We found that the proliferation of murine B16F0 melanoma cells, their colony formation on soft agar, and growth of transplanted melanoma in vivo are clearly inhibited by the introduction of NCAM siRNA. Interestingly, change of NCAM expression level is shown to regulate the activity of Wnt signaling molecule, β-catenin, markedly. This novel machinery requires the function of FGF receptor and glycogen synthase kinase-3β but is independent of the Wnt receptors, MAPK-Erk and PI3K/Akt pathways. In addition, NCAM is found to form a functional complex with β-catenin, FGF receptor, and glycogen synthase kinase-3β. Moreover, up-regulation of NCAM140 and NCAM180 appears more potent than NCAM120 in activation of β-catenin, suggesting that the intracellular domain of NCAM is required for facilitating the β-catenin signaling. Furthermore, the melanoma cells also exhibit distinct differentiation phenotypes with the NCAM silencing. Our findings reveal a novel regulatory role of NCAM in the progression of melanoma that might serve as a new therapeutic target for the treatment of melanoma.
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Hai Jie
authors.initials: HJ
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Yin Yan
authors.initials: YY
authors.lastname: Xia
authors.forename: Jing Lin Jack
authors.initials: JL
authors.lastname: Wong
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Feng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3