title: Podocalyxin promotes glioblastoma multiforme cell invasion and proliferation via β-catenin signaling.
abstract: Both podocalyxin (PODX) and β-catenin (β-cat) signaling reportedly play important roles in glioblastoma multiforme (GBM) progression. In this study, we for the first time explored crosstalk between PODX and β-cat signaling in GBM cells, and assessed its impact on GBM cell invasion and proliferation. Stable overexpression of PODX in LN-229 and U-118 MG human GBM cells increased the soluble/intracellular β-cat level, TOPflash luciferase reporter activity, the mRNA levels of β-cat signaling target genes, matrix metalloproteinase 9 (MMP9) expression/activity, and cell invasion and proliferation, which was abolished by selective p38 mitogen-activated protein kinase (MAPK) inhibitor PD169316 and selective β-cat signaling inhibitor CCT031374. On the other hand, stable knockdown of PODX in LN-229 and U-118 MG cells decreased the soluble β-cat level, TOPflash luciferase reporter activity, the mRNA levels of β-cat signaling target genes, MMP9 expression/activity, and cell invasion and proliferation, which was completely reversed by overexpression of a constitutively active β-cat mutant. In addition, overexpression of PODX induced p38 MAPK activity and inactivating phosphorylation of glycogen synthase kinase-3β (GSK-3β) at serine 389 in LN-229 and U-118 MG cells, which was abolished by PD169316, but not CCT031374; knockdown of PODX decreased p38 MAPK activity and inactivating phosphorylation of GSK-3β at serine 389 in both cell lines, which was not significantly affected by overexpression of constitutively active β-cat. In conclusion, this study indicates that PODX promotes GBM cell invasion and proliferation by elevating the soluble β-cat level/β-cat signaling through the p38 MAPK/GSK-3β pathway. Uncovering the PODX/β-cat signaling axis adds new insights not only into the biological functions of PODX and β-cat, but also into the molecular mechanisms underlying GBM progression.
authors.affiliation: Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Jiang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D012795:Sialoglycoproteins; D051176:beta Catenin; C001643:podocalyxin