# The Cytoskeleton in Adrenal Physiology and Tumours: Functional Roles and Emerging Molecular Targets

## TL;DR

This review explores how the cytoskeleton regulates adrenal function and contributes to adrenal cancer, identifying potential targets for treatment.

## Contribution

The first comprehensive review on the cytoskeleton's role in adrenal physiology and tumorigenesis.

## Key findings

- Cytoskeletal proteins like cofilin and DIAPH1 influence steroidogenesis by regulating cholesterol transfer.
- Dysregulation of FLNA, FSCN1, and VAV2 correlates with aggressive adrenocortical carcinoma traits.
- Cytoskeleton-related proteins offer promising therapeutic targets for adrenal cancer treatment.

## Abstract

The cytoskeleton has been described as a regulator of adrenal physiology and tumour behaviour. In the adrenal cortex, both cytoskeletal filaments, by mediating cholesterol transfer to mitochondria, and their binding proteins, such as cofilin and diaphanous-related formin 1 (DIAPH1), have been implicated in modulating steroidogenic processes. Beyond hormone production, the cytoskeleton participates in oncogenic signalling and contributes to the acquisition of malignant behaviour in adrenocortical carcinoma (ACC). Cytoskeleton-associated proteins such as filamin A (FLNA), fascin-1 (FSCN1), RASSF1A, and the guanine nucleotide exchange factor VAV2 are involved in signal transduction, cell cycle regulation, and cytoskeletal remodelling. In ACC, dysregulation of the expression or activity of these proteins correlates with ACC aggressiveness, including increased proliferation, motility, and invasion as well as poor prognosis, making them attractive candidates for targeted therapeutic strategies. To date, no review has systematically addressed the role of cytoskeleton and its binding partners in both adrenal physiological regulation and pathological context. This review is the first to provide a comprehensive overview of cytoskeletal involvement in adrenal cortex function and cancer, highlighting emerging molecular players and their possible therapeutic implications.