title: N-myc downstream regulated gene 1 modulates Wnt-β-catenin signalling and pleiotropically suppresses metastasis.
abstract: Wnt signalling has pivotal roles in tumour progression and metastasis; however, the exact molecular mechanism of Wnt signalling in the metastatic process is as yet poorly defined. Here we demonstrate that the tumour metastasis suppressor gene, NDRG1, interacts with the Wnt receptor, LRP6, followed by blocking of the Wnt signalling, and therefore, orchestrates a cellular network that impairs the metastatic progression of tumour cells. Importantly, restoring NDRG1 expression by a small molecule compound significantly suppressed the capability of otherwise highly metastatic tumour cells to thrive in circulation and distant organs in animal models. In addition, our analysis of clinical cohorts data indicate that Wnt+/NDRG-/LRP+ signature has a strong predictable value for recurrence-free survival of cancer patients. Collectively, we have identified NDRG1 as a novel negative master regulator of Wnt signalling during the metastatic progression, which opens an opportunity to define a potential therapeutic target for metastatic disease.
authors.affiliation: Department of Medical Microbiology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.forename: Megumi
authors.initials: M
authors.lastname: Iiizumi-Gairani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okuda
authors.forename: Misako
authors.initials: M
authors.lastname: Watabe
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Pai
authors.forename: Puspa R
authors.initials: PR
authors.lastname: Pandey
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hirota
authors.forename: Aya
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Yin-Yuan
authors.initials: YY
authors.lastname: Mo
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016259:Genes, myc; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000099259:N-myc Downstream-Regulated Gene 1 Protein