FAM107A Inactivation Associated with Promoter Methylation Affects Prostate Cancer Progression through the FAK/PI3K/AKT Pathway

Simple Summary Prostate cancer (PCa) is a common male malignancy. FAM107A, or actin-associated protein, is commonly downregulated in PCa and is associated with a poor patient prognosis. We investigated the role of FAM107A in PCa and found that downregulation of FAM107A expression was caused by hypermethylation of CpG islands, and DNA methyltransferase 1 (DNMT1) was involved in maintaining hypermethylation. Mechanistically, FAM107A regulated PCa cell growth through the FAK/PI3K/AKT signaling pathway. Therefore, FAM107A overexpression may represent a potential treatment for PCa, while therapies targeting epigenetic events that regulate FAM107A expression may also be an effective strategy for PCa treatment. Prostate cancer (PCa) is one of the most common cancers and is the second leading cause of mortality in men. Studies exploring novel therapeutic methods are urgently needed. FAM107A, a coding gene located in the short arm of chromosome3, is generally downregulated in PCa and is associated with a poor prognosis. However, the downregulation of FAM107A in PCa and the mechanism of its action remain challenging to determine. This investigation found that downregulation of FAM107A expression in PCa was caused by hypermethylation of CpG islands. Furthermore, DNA methyltransferase 1 (DNMT1) was involved in maintaining hypermethylation. Mechanistically, overexpression of FAM107A inhibits tumor cell proliferation, migration, invasion and promotes apoptosis through the FAK/PI3K/AKT signaling pathway, indicating that FAM107A may be a molecular brake of FAK/PI3K/AKT signaling, thus limiting the active state of the FAK/PI3K/AKT pathway. These findings will contribute to a better understanding of the effect of FAM107A in PCa, and FAM107A may represent a new therapeutic target for PCa.