# Actin-Like Protein 6A as an Oncogene and Therapeutic Target in Cancer

## TL;DR

This paper reviews how ACTL6A, a protein involved in chromatin remodeling, acts as an oncogene in various cancers and explores its potential as a therapeutic target.

## Contribution

The paper systematically integrates evidence across multiple cancer types to clarify ACTL6A's oncogenic mechanisms and therapeutic potential.

## Key findings

- ACTL6A overexpression promotes tumor progression and metastasis through chromatin remodeling and signaling pathway crosstalk.
- ACTL6A correlates with poor prognosis and therapy resistance in cancers like hepatocellular carcinoma and breast cancer.
- Strategies to inhibit ACTL6A, such as siRNA and small-molecule inhibitors, are discussed for therapeutic development.

## Abstract

ACTL6A, a core subunit of the SWI/SNF chromatin remodeling complex, has emerged as a critical oncogenic driver across multiple malignancies. Recent studies reveal that aberrant ACTL6A overexpression promotes tumor initiation, progression, and metastasis by orchestrating chromatin remodeling, transcriptional reprogramming, and crosstalk with key signaling pathways (e.g., Hippo/YAP, Notch, and PI3K/AKT). This review systematically synthesizes evidence from in vitro, in vivo, and clinical studies spanning hepatocellular carcinoma, breast cancer, glioblastoma, and 10 other cancer types, highlighting ACTL6A's dual role as a chromatin remodeler and an independent oncogenic effector. Key mechanisms include sustaining cancer stemness, suppressing apoptosis, enhancing DNA repair, and driving metabolic reprogramming. Clinically, ACTL6A overexpression correlates with advanced tumor stage, therapy resistance, and poor prognosis, positioning it as a promising prognostic biomarker and therapeutic target. We further discuss emerging strategies to inhibit ACTL6A (e.g., siRNA, small-molecule inhibitors) and propose combinatorial approaches to overcome drug resistance. By integrating multi-omics data and preclinical models, this review not only clarifies ACTL6A's context-dependent oncogenic networks but also bridges mechanistic insights to translational challenges, offering a roadmap for future research and therapeutic development.