# Dual Role of HNF4α in Colorectal Adenocarcinoma During Carcinogenesis and Metastasis

## TL;DR

HNF4α plays a dual role in colorectal cancer, promoting early tumor growth but inhibiting metastasis later on.

## Contribution

The study reveals HNF4α's dual function in CRAC progression and metastasis through its interaction with NF-κb and YAP pathways.

## Key findings

- HNF4α is upregulated during early carcinogenesis but reduced in metastatic and poorly differentiated CRAC.
- HNF4α overexpression promotes migration and invasion, while its inhibition suppresses these processes.
- Reduced HNF4α levels correlate with poor prognosis and increased NF-κb and YAP activity.

## Abstract

Hepatocyte nuclear factor 4α (HNF4α), a highly conserved member of the nuclear receptor superfamily of transcription factors, has been identified as a promising therapeutic candidate for colorectal adenocarcinoma (CRAC). This study was to investigate the significance of HNF4α in CRAC and mechanisms governing its function. The expression patterns and clinical relevance of HNF4α were evaluated in relation to nuclear factor kappa B (NF-κb), Yes-associated protein (YAP), and epithelial–mesenchymal transition markers. HNF4α exhibited upregulation during carcinogenesis compared to normal and precancerous lesions. The overexpression and inhibition of HNF4α were correlated with the modulation of CRAC cell migration and invasion, either promoting or suppressing these processes. Notably, levels of HNF4α were significantly diminished in metastatic and poorly differentiated CRAC relative to primary CRAC samples. Moreover, reduced HNF4α levels were associated with unfavorable prognostic factors. The inhibition of HNF4A induced a decrease in NF-κb protein levels, concomitant with an increase in YAP. Our results indicate a dual role of HNF4α in tumor progression, either as a promotor or inhibitor, depending on the pathologic condition of CRAC and the related signaling pathways. HNF4α exhibits a complex role, whereby its overexpression is linked to early carcinogenesis and reduced expression is associated with the progression and metastasis of CRAC.