Unknown

Dataset Information

0

NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer.


ABSTRACT: The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and metastatic properties. This aggressive phenotype remains poorly understood. We have recently identified neuroepithelial cell transforming gene 1 (NET1), a guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial cell transforming gene 1 expression is enhanced in GA and it is of functional importance in cell invasion. In this study, we demonstrate the activity of NET1 in driving cytoskeletal rearrangement, a key pathological mechanism in gastric tumour cell migration and invasion. Neuroepithelial cell transforming gene 1 expression was increased 10-fold in response to treatment with lysophosphatidic acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold increase in cell invasion. Lysophosphatidic acid-induced cell invasion and migration were significantly inhibited using either NET1 siRNA or a RhoA inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in gastric cancer progression. Furthermore, LPA-induced invasion and migration were also significantly reduced in the presence of cytochalasin D, an inhibitor of cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown resulted in AGS cell rounding and a loss of actin filament organisation, demonstrating the function of NET1 in actin organisation. These data highlight the importance of NET1 as a driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation.

SUBMITTER: Murray D 

PROVIDER: S-EPMC2570507 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC8024553 | biostudies-literature
| S-EPMC6559315 | biostudies-literature
| S-EPMC3572452 | biostudies-other
| S-EPMC2782020 | biostudies-literature
| S-EPMC4385928 | biostudies-literature
2011-01-02 | GSE26309 | GEO
2011-01-02 | E-GEOD-26309 | biostudies-arrayexpress
| S-EPMC3566084 | biostudies-literature
| S-EPMC6458266 | biostudies-literature
| S-EPMC5732804 | biostudies-literature