# Ankrd1 Promotes Lamellipodia Formation and Cell Motility via Interaction with Talin-1 in Clear Cell Renal Cell Carcinoma

## TL;DR

Ankrd1 promotes cell movement in kidney cancer by forming lamellipodia and interacting with talin-1, contributing to cancer progression.

## Contribution

This study identifies Ankrd1 as a novel regulator of cell motility in clear cell renal cell carcinoma via lamellipodia formation and talin-1 interaction.

## Key findings

- High Ankrd1 expression correlates with poor prognosis in clear cell renal cell carcinoma patients.
- Ankrd1 regulates cell motility and lamellipodia formation in ccRCC cells.
- Ankrd1 interacts with talin-1 and modulates integrin pathway activation in lamellipodia.

## Abstract

Ankyrin repeat domain 1 (Ankrd1), a transcriptional target of Yes-associated protein (YAP), is linked to cardiomyopathy. However, its role in cancer, particularly in clear cell renal cell carcinoma (ccRCC), remains vague. In this study, we examined the expression, regulation, and function of Ankrd1 in ccRCC. High Ankrd1 expression was related to poor prognosis in patients with ccRCC in The Cancer Genome Atlas cohort. Ankrd1 expression was regulated by YAP in all ccRCC cell lines examined and also by ERK5 in a subset of ccRCC cell lines. Moreover, silencing of Ankrd1 in ccRCC cell lines resulted in decreased cell motility, whereas its overexpression increased the cell motility. Ankrd1 colocalized with F-actin in lamellipodia upon phorbol ester stimulation. Ankrd1 silencing resulted in alterations in the shape of RCC cells and caused a decrease in lamellipodia formation. Ankrd1 also colocalized with talin-1 in lamellipodia. Ankrd1 depletion repressed talin-1-mediated activation of the integrin pathway. Immunohistochemical examination of surgical specimens revealed high expression of Ankrd1 in metastatic RCC tissues compared with that in primary RCC tissues from the same patients. Collectively, these findings suggest that Ankrd1 plays a critical role in the motility of ccRCC cells through lamellipodia formation.