Genes & Cancer

Impairement of HT29 cancer cells cohesion by the soluble form of neurotensin receptor-3

Fabienne Massa1,*, Christelle Devader1,*, Sandra Lacas-Gervais2, Sophie Béraud-Dufour1, Thierry Coppola1 and Jean Mazella1

1 Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice-Sophia Antipolis, Valbonne, France.

2 Centre Commun de Microscopie Appliquée, Université de Nice-Sophia Antipolis, Nice, France

* These authors contributed equally to the work


Jean Mazella, email:

Keywords: soluble sortilin, cell morphology, desmosomes, cancer, neurotensin

Received: June 3, 2014 Accepted: July 25, 2014 Published: July 27, 2014


The neurotensin (NT) receptor-3 (NTSR3), also called sortilin is a multifunctional protein localized at the intracellular and plasma membrane level. The extracellular domain of NTSR3 (sNTSR3) is released by shedding from several cell lines including colonic cancer cells. This soluble protein acts as an active ligand through its ability to bind, to be internalized in the human adenocarcinoma epithelial HT29 cells and to stimulate the PI3 kinase pathway. The aim of this study was to investigate cellular responses induced by sNTSR3 in HT29 cells. The cellular functions of sNTSR3 were monitored by immunofluocytochemistry, electron microscopy and quantitative PCR in order to characterize the cell shape and the expression of adhesion proteins. We evidenced that sNTSR3 significantly regulates the cellular morphology as well as the cell-cell and the cell-matrix adherens properties by decreasing the expession of several integrins and by modifying the structure of desmosomes. Altogether, these properties lead to an increase of cell detachment upon sNTSR3 treatment on HT29, HCT116 and SW620 cancer cells. Our results indicate that sNTSR3 may induce the first phase of a process which weaken HT29 epithelial properties including desmosome architecture, cell spreading, and initiation of cell separation, all events which could be responsible for cancer metastasis.

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