Abstract
Simple SummaryBRCA1 has critical functions in accurately repairing double stand breaks in the DNA through a process known as homologous recombination. BRCA1 also has various functions in other cellular processes that safeguard the genome. Thus, mutations or silencing of this tumor suppressor significantly increases the risk of developing breast, ovarian, and other cancers. Metastasis refers to the spread of cancer to other parts of the body and is the leading cause of cancer-related deaths. In this review, we discuss the mechanisms by which BRCA1 mutations contribute to the metastatic and aggressive nature of the tumor cells.Heritable mutations in BRCA1 and BRCA2 genes are a major risk factor for breast and ovarian cancer. Inherited mutations in BRCA1 increase the risk of developing breast cancers by up to 72% and ovarian cancers by up to 69%, when compared to individuals with wild-type BRCA1. BRCA1 and BRCA2 (BRCA1/2) are both important for homologous recombination-mediated DNA repair. The link between BRCA1/2 mutations and high susceptibility to breast cancer is well established. However, the potential impact of BRCA1 mutation on the individual cell populations within a tumor microenvironment, and its relation to increased aggressiveness of cancer is not well understood. The objective of this review is to provide significant insights into the mechanisms by which BRCA1 mutations contribute to the metastatic and aggressive nature of the tumor cells.
Highlights
Breast cancer susceptibility gene 1 (BRCA1) encodes the tumor suppressor BRCA1, which was first linked to hereditary breast and ovarian cancer in the early 1990s [1]
Though this study reported that central nervous system (CNS) metastases were observed at comparable frequencies in both BRCA1- and BRCA2-mutation carriers, when adjusting for breast cancer subtypes, a significant association with CNS metastases was primarily observed in BRCA2 mutation carriers
It is well known that BRCA1 functions to maintain genome stability, it is evident that BRCA1 plays an important role in cancer cell metastasis by regulating epithelial to mesenchymal transition (EMT), apicobasal polarity, and the tumor microenvironment
Summary
Breast cancer susceptibility gene 1 (BRCA1) encodes the tumor suppressor BRCA1, which was first linked to hereditary breast and ovarian cancer in the early 1990s [1]. Given the critical role of BRCA1 in the repair of DNA double-strand breaks via the error-free homologous recombination (HR) pathway and its additional roles in other cellular processes that safeguard genomic integrity, it is not surprising that mutations in this tumor suppressor gene considerably increase cancer risk (Figure 1) [6,7]. Therapeutic strategies that benefit cancer patients with BRCA1/2-mutant tumors have shown promising results in targeting tumors with mutations in other genes necessary for HR [10]. A. Cancers 2022, 14, 108 recent study has reported that germline BRCA1 mutations in breast cancer patients appear to be associated with an increased risk of brain metastasis even when accounting for other confounding factors, such as age and stage [20]. Understanding cancer cell behavior and associated tissue alterations that arise as a result of loss of BRCA1 function may help improve current therapeutic strategies employed to treat BRCA1 mutant cancers
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