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Exp Cell Res. 2018 Jan 15;362(2):498-503. doi: 10.1016/j.yexcr.2017.12.014. Epub 2017 Dec 15.

By modulating α2β1 integrin signalling, gastrin increases adhesion oF AGS-GR gastric cancer cells.

Author information

1
INSERM UMR.1037-Cancer Research Center of Toulouse (CRCT)/University Paul Sabatier Toulouse III, team 11, Oncopole 2 Avenue Hubert Curien, CS 53717, 31037 Toulouse, France.
2
INSERM UMR.1037-Cancer Research Center of Toulouse (CRCT)/University Paul Sabatier Toulouse III, team 11, Oncopole 2 Avenue Hubert Curien, CS 53717, 31037 Toulouse, France; IUCT-oncopole Toulouse, France.
3
INSERM UMR.1037-Cancer Research Center of Toulouse (CRCT)/University Paul Sabatier Toulouse III, team 11, Oncopole 2 Avenue Hubert Curien, CS 53717, 31037 Toulouse, France. Electronic address: cathy.seva@inserm.fr.

Abstract

Peritoneal metastasis is a major cause of recurrence of gastric cancer and integrins are key molecules involved in gastric cancer cells attachment to the peritoneum. The peptide hormone, gastrin, initially identified for its role in gastric acid secretion is also a growth factor for gastric mucosa. Gastrin has also been shown to contribute to gastric cancers progression. Here, we provide the first evidence that gastrin increases the adhesion of gastric cancer cells. Gastrin treatment induces the expression of α2 integrin subunit through a mechanism that involves the ERK pathway. We also observed in response to gastrin an increase in the amount of α2 integrin associated with β1subunit. In addition, gastrin-stimulated cell adhesion was blocked with an anti-α2β1 integrin neutralizing antibody. We also show that gastrin activates the integrin pathway via the phosphorylation of β1 integrin by a Src family kinase. This mechanism may contribute to the enhancement of cell adhesion observed in response to gastrin since we found an inhibition of gastrin-mediated cell adhesion when cells were treated with a Src inhibitor. By regulating one of the key step of the metastatic process gastrin might contribute to increase the aggressive behaviour of human gastric tumours.

KEYWORDS:

Cell adhesion; Gastric cancer; Gastrin; Integrins; Metastasis

PMID:
29253536
DOI:
10.1016/j.yexcr.2017.12.014
[Indexed for MEDLINE]

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