FOXA2 suppresses the metastasis of hepatocellular carcinoma partially through matrix metalloproteinase-9 inhibition.

Carcinogenesis

Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China and Department of Internal Medicine, Chinese PLA 531 Hospital, Tonghua 134000, Jilin, China

Published: November 2014

The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues. Clinicopathological analysis revealed that reduced FOXA2 expression was correlated with aggressive characteristics (venous invasion, poor differentiation, high tumor node metastasis grade). FOXA2 level was even lower in portal vein tumor thrombus compared with primary tumor tissues and correlated with epithelial-mesenchymal transition in HCC cells. Overexpression of FOXA2 inhibited migration and invasion of Focus cells, whereas knockdown of FOXA2 in HepG2 showed the opposite effect. Moreover, upregulation of FOXA2 suppressed HCC metastasis to bone, brain and lung in two distinct mouse models. Finally, we proved that FOXA2 repressed the transcription of matrix metalloproteinase (MMP)-9 and exerted its antimetastasis effect partially through downregulation of MMP-9. In conclusion, our findings indicate that FOXA2 plays a critical role in HCC metastasis and may serve as a novel therapeutic target for HCC.

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgu180DOI Listing

Publication Analysis

Top Keywords

foxa2
10
metastasis hepatocellular
8
hepatocellular carcinoma
8
hcc metastasis
8
hcc
6
metastasis
5
foxa2 suppresses
4
suppresses metastasis
4
carcinoma partially
4
partially matrix
4

Similar Publications

Knockdown of HOXD13 in Oral Squamous Cell Carcinoma Inhibited its Proliferation, Migration, and Influenced Fatty Acid Metabolism.

J Cancer

January 2025

Department of Oral and Maxillofacial Surgery, School of Stomatology, Hebei Medical University, Hebei Technology Innovation Center of Oral Health, Key Laboratory of Stomatology and Clinical Research Centre for Oral Diseases, Hebei Province, Shijiazhuang, 050017, China.

HOXD13, a member of the homeobox gene family, plays a critical role in developmental processes and has been implicated in various malignancies, including pancreatic cancer and glioma. However, its role in oral squamous cell carcinoma (OSCC) remains poorly understood. This study aimed to elucidate the potential of HOXD13 as a diagnostic biomarker and therapeutic target for OSCC.

View Article and Find Full Text PDF

Hypoxia-caused spermatogenesis impairment may contribute to male infertility. FOXA2 has been found to be abundant in spermatogonial stem cells and critical for spermatogenesis. Here we aimed to explore the roles of FOXA2 in regulating spermatogonial cells against hypoxia stimulation.

View Article and Find Full Text PDF

Neuroendocrine prostate cancer (NEPC), an aggressive and lethal subtype of prostate cancer (PCa), often arises as a resistance mechanism in patients undergoing hormone therapy for prostate adenocarcinoma. NEPC is associated with a significantly poor prognosis and shorter overall survival compared to conventional prostate adenocarcinoma due to its aggressive nature and limited response to standard of care therapies. This transdifferentiation, or lineage reprogramming, to NEPC is characterised by the loss of androgen receptor (AR) and prostate-specific antigen (PSA) expression, and the upregulation of neuroendocrine (NE) biomarkers such as neuron-specific enolase (NSE), chromogranin-A (CHGA), synaptophysin (SYP), and neural cell adhesion molecule 1 (NCAM1/CD56), which are critical for NEPC diagnosis.

View Article and Find Full Text PDF

A significant number of castration-resistant prostate cancer (CRPC) evolve into a neuroendocrine (NE) subtype termed NEPC, leading to resistance to androgen receptor (AR) pathway inhibitors and poor clinical outcomes. Through Hi-C analyses of a panel of patient-derived xenograft tumors, here we report drastically different 3D chromatin architectures between NEPC and CRPC samples. Such chromatin re-organization was faithfully recapitulated in vitro on isogenic cells undergoing NE transformation (NET).

View Article and Find Full Text PDF

Cellular differentiation is controlled by intricate layers of gene regulation, involving the modulation of gene expression by various transcriptional regulators. Due to the complexity of gene regulation, identifying master regulators across the differentiation trajectory has been a longstanding challenge. To tackle this problem, a computational framework, single-cell Boolean network inference and control (BENEIN), is presented.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!