# FOXD1, a hypoxia-related gene, accelerates prostate cancer cell growth by increasing glycolysis under hypoxia conditions

## TL;DR

FOXD1, a gene linked to low oxygen conditions, promotes prostate cancer growth by boosting glycolysis in hypoxic environments.

## Contribution

This study reveals a novel role of FOXD1 in accelerating prostate cancer cell growth through enhanced glycolysis under hypoxia.

## Key findings

- FOXD1 expression is upregulated in prostate cancer and promotes cell viability and colony formation under normoxia and hypoxia.
- FOXD1 knockdown reduces hypoxia-induced glycolysis markers like lactate production and glucose consumption.
- Inhibiting glycolysis reverses the growth-promoting effects of FOXD1 overexpression in hypoxic prostate cancer cells.

## Abstract

Hypoxia is a key feature of the tumor microenvironment, and can promote tumor progression. FOXD1 has been found to be involved in several types of cancer; however, its role in mediating cancer cell growth under hypoxia conditions is unclear. In this study, we aimed to test the effect of FOXD1 on prostate cancer cell growth in response to hypoxia. Our results showed that FOXD1 expression was upregulated in prostate cancer. Under normoxia conditions, FOXD1 knockdown inhibited prostate cancer cell viability and colony formation, while FOXD1 overexpression exhibited the opposite effects. Hypoxia exposure increased the expression of FOXD1 in prostate cancer. FOXD1 knockdown inhibited hypoxia-induced increase in cell viability and colony formation ability, whereas FOXD1 overexpression showed the opposite effects. In addition, FOXD1 knockdown inhibited hypoxia-induced increase in lactate production, glucose consumption, and the expression levels of HK-2 and LDHA. Moreover, inhibition of glycolysis by 2-deoxyglucose reversed the effect of FOXD1 overexpression on hypoxia-induced prostate cancer cell growth. These results indicated that hypoxia-induced FOXD1 expression accelerated glycolysis, ultimately promoting prostate cancer cell growth.

The online version contains supplementary material available at 10.1186/s12896-025-01061-6.