# Reduced RhoGDI2 Expression Disrupts Centrosome Functions and Promotes Mitotic Errors

## TL;DR

Reduced RhoGDI2 expression disrupts centrosome functions and immune synapses, contributing to cancer progression and immune cell dysfunction.

## Contribution

This study reveals novel roles for RhoGDI2 in centrosome regulation and immune synapse formation in cancer.

## Key findings

- RhoGDI2 suppression reduces cancer cell proliferation and causes supernumerary centrosomes.
- RhoA silencing partially rescues centrosome and ciliary defects caused by RhoGDI2 knockdown.
- RhoGDI2 silencing in NK cells impairs immune synapse-related cancer cell-killing activity.

## Abstract

RhoGDI2 is a RhoGTPase regulator that has roles in cytoskeleton organization and cell survival, amongst others. It is differentially expressed in many cell types and tissues, including several human cancers, where its expression has been correlated with either good or bad prognosis. To identify the underlying mechanisms, we knocked down its expression in human cancer cell lines. We observed that repression of RhoGDI2 expression, but not that of the closely related RhoGDI1, significantly reduces their proliferation rate. In parallel, RhoGDI2 suppression induces supernumerary centrosomes and inhibits ciliogenesis. As RhoGDIs are regulators of GTPases, we checked whether key RhoGTPases are involved in these effects. We found that silencing RhoA partially rescued the induction of supernumerary centrosomes and ciliary defects observed upon RhoGDI2 silencing. It was previously shown that RhoGDI2 is strongly expressed in immune cells and that there are striking similarities between primary cilia and immune synapses. Based on this knowledge, we silenced RhoGDI2 in NK cells and could demonstrate that this strongly affects their immune synapse-related cancer cell-killing activity. Altogether, these data suggest novel roles for RhoGDI2 in centrosome functions in human cancer and immune synapses in immune cells, which provides an explanation for its reported dual role in cancer.