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Biochem J. 2017 Nov 1;474(22):3733-3746. doi: 10.1042/BCJ20170348.

Depletion of MUC5B mucin in gastrointestinal cancer cells alters their tumorigenic properties: implication of the Wnt/β-catenin pathway.

Lahdaoui F1,2,3, Messager M1,2,3,4, Vincent A1,2,3, Hec F1,2,3,4, Gandon A1,2,3,4, Warlaumont M1,2,3,4, Renaud F1,2,3,5, Leteurtre E1,2,3,5, Piessen G1,2,3,4, Jonckheere N1,2,3, Mariette C1,2,3,4, Van Seuningen I6,2,3.

Author information

1
Univ. Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences and Cancer, Lille F-59000, France.
2
Inserm, UMR-S 1172, Team 'Mucins, Epithelial Differentiation and Carcinogenesis', Lille F-59000, France.
3
CHU Lille, Lille F-59000, France.
4
Department of Digestive and Oncological Surgery, Claude Huriez Hospital, CHU Lille, Lille F-59000, France.
5
Pathology Institute, Biology Pathology Center, CHU Lille, Lille F-59000, France.
6
Univ. Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences and Cancer, Lille F-59000, France isabelle.vanseuningen@inserm.fr.

Abstract

Secreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosae in normal adults. Alteration of their expression is a hallmark of numerous epithelial cancers and has often been correlated to bad prognosis of the tumour. The secreted mucin MUC5B is overexpressed in certain subtypes of gastric and intestinal cancers, but the consequences of this altered expression on the cancer cell behaviour are not known. To investigate the role of MUC5B in carcinogenesis, its expression was knocked-down in the human gastric cancer cell line KATO-III and in the colonic cancer cell line LS174T by using transient and stable approaches. Consequences of MUC5B knocking-down on cancer cells were studied with respect to in vitro proliferation, migration and invasion, and in vivo on tumour growth using a mouse subcutaneous xenograft model. Western blotting, luciferase assay and qRT-PCR were used to identify proteins and signalling pathways involved. In vitro MUC5B down-regulation leads to a decrease in proliferation, migration and invasion properties in both cell lines. Molecular mechanisms involved the alteration of β-catenin expression, localization and activity and decreased expression of several of its target genes. In vivo xenografts of MUC5B-deficient cells induced a decrease in tumour growth when compared with MUC5B-expressing Mock cells. Altogether, the present study shows that down-regulation of MUC5B profoundly alters proliferation, migration and invasion of human gastrointestinal cancer cells and that these alterations may be, in part, mediated by the Wnt/β-catenin pathway emphasizing the potential of MUC5B as an actor of gastrointestinal carcinogenesis.

KEYWORDS:

MUC5B; Wnt signalling pathway; cell proliferation; gastrointestinal cancer; mucin; tumour growth

PMID:
28972071
DOI:
10.1042/BCJ20170348
[Indexed for MEDLINE]

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