AUTHOR=Kaljunen Heidi , Taavitsainen Sinja , Kaarijärvi Roosa , Takala Eerika , Paakinaho Ville , Nykter Matti , Bova G. Steven , Ketola Kirsi 

TITLE=Fanconi anemia pathway regulation by FANCI in prostate cancer

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1260826

DOI=10.3389/fonc.2023.1260826

ISSN=2234-943X

ABSTRACT=<p>Prostate cancer is one of the leading causes of death among men worldwide, and thus, research on the genetic factors enabling the formation of treatment-resistant cancer cells is crucial for improving patient outcomes. Here, we report a cell line-specific dependence on <italic>FANCI</italic> and related signaling pathways to counteract the effects of DNA-damaging chemotherapy in prostate cancer. Our results reveal that <italic>FANCI</italic> depletion results in significant downregulation of Fanconi anemia (FA) pathway members in prostate cancer cells, indicating that <italic>FANCI</italic> is an important regulator of the FA pathway. Furthermore, we found that FANCI silencing reduces proliferation in p53-expressing prostate cancer cells. This extends the evidence that inactivation of <italic>FANCI</italic> may convert cancer cells from a resistant state to an eradicable state under the stress of DNA-damaging chemotherapy. Our results also indicate that high expression of FA pathway genes correlates with poorer survival in prostate cancer patients. Moreover, genomic alterations of FA pathway members are prevalent in prostate adenocarcinoma patients; mutation and copy number information for the FA pathway genes in seven patient cohorts (N = 1,732 total tumor samples) reveals that 1,025 (59.2%) tumor samples have an alteration in at least one of the FA pathway genes, suggesting that genomic alteration of the pathway is a prominent feature in patients with the disease.</p>