Here, we report that LRH-1, which exhibited an increased expression pattern in high-grade prostate cancer and CRPC xenograft models, functions to promote <i>de novo</i> androgen biosynthesis via its direct transactivation of several key steroidogenic enzyme genes, elevating intratumoral androgen levels and reactivating AR signaling in CRPC xenografts as well as abiraterone-treated CRPC tumors.
Preclinical studies in several tumour models have shown that P2X7R targeting is potentially a very effective anticancer treatment, and many pharmaceutical companies have now developed potent and selective small molecule inhibitors of P2X7R.
Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that is highly expressed in a variety of cancer tissues, promotes tumor cell proliferation and metastasis, and is involved in the tumor cell cycle and apoptosis.
The effects of purinergic receptor stimulation or agonism tend to produce inflammatory responses that may aid immune stimulation but may also provoke various immune suppression mechanisms, particularly in the tumor microenvironment.
These significant associations of LRH-1 protein expression with tumour phenotype suggest that LRH-1 is an important indicator of tumour biology in breast cancers and may be useful in risk stratification.
Herein, we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies.
These results suggest that the efficacy of BBG in inhibiting tumor growth is primarily mediated by direct actions of the compound on P2X7R in glioma cells and that pharmacological inhibition of this purinergic receptor might serve as a strategy to slow the progression of brain tumors.