# Transcriptional factor ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation

## TL;DR

This study shows that the ZMYM3 protein helps liver cancer spread by boosting CTTN and forming structures that aid invasion.

## Contribution

ZMYM3's role in promoting HCC metastasis through CTTN upregulation and invadopodia formation is newly identified.

## Key findings

- ZMYM3 is upregulated in HCC tissues and linked to recurrence and poor prognosis.
- ZMYM3 enhances HCC cell invasion and metastasis by promoting invadopodia and EMT.
- ZMYM3 directly binds to the CTTN promoter, increasing its expression and metastatic potential.

## Abstract

Hepatocellular carcinoma (HCC) is characterized by high invasiveness and metastatic potential, leading to poor prognosis. Therefore, understanding the molecular mechanisms underlying HCC invasion and metastasis is essential for developing effective therapeutic strategies. This study investigates the role of ZMYM3 in HCC invasion and metastasis. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, along with immunohistochemistry, revealed that ZMYM3 is upregulated in HCC tissues and associated with recurrence and poor prognosis. Single-cell sequencing data indicated higher ZMYM3 expression in portal vein tumor thrombus compared to primary lesions, suggesting its involvement in metastasis. Functional assays demonstrated that ZMYM3 enhances HCC cell proliferation, invasion, and metastasis. RNA sequencing identified that ZMYM3 promotes invadopodia formation and epithelial-mesenchymal transition (EMT) in HCC cells. Further chromatin immunoprecipitation sequencing and mechanistic studies showed that ZMYM3 directly binds to the promoter of CTTN, a key gene regulating invadopodia formation, thereby increasing its expression. This upregulation contributes to the enhanced invasive and metastatic capabilities of HCC cells. Our findings identify ZMYM3 overexpression as a predictor of high recurrence risk and poor prognosis in HCC patients. Mechanistically, ZMYM3 promotes invadopodia formation primarily through the upregulation of CTTN, thereby augmenting the invasive and metastatic potential of HCC cells. These results highlight the critical role of ZMYM3 in HCC progression and metastasis.

ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation.

ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation.