Recurrent
metastasis is a major fatal cause of
breast cancer. Regretfully, the driving force and the molecular beneath have not been fully illustrated yet. In this study, a cohort of
breast cancer patients with locoregional
metastasis was recruited. For them, we collected the matched samples of the primary
tumor and metastatic
tumor, and then we determined the mutation profiles with whole-exome sequencing (WES). On basis of the profiles, we identified a list of deleterious variants in eight susceptible genes. Of them,
filamin A (FLNA) was considered a potential driver gene of
metastasis, and its low expression could enhance 5 years' relapse survival rate by 15%. To prove the finding, we constructed a stable FLNA knockout tumor cell line, which manifested that the cell abilities of proliferation, migration, and invasion were significantly weakened in response to the gene knockout. Subsequently, xenograft mouse experiments further proved that FLNA knockout could inhibit local or distal
metastasis. Putting all the results together, we consolidated that FLNA could be a potential driver gene to
metastasis of
breast cancer, in particular
triple-negative breast cancer. Additional experiments also suggested that FLNA might intervene in
metastasis via the regulation of MMP-1 expression. In summary, this study demonstrates that FLNA may play as a positive regulator in
cancer proliferation and recurrence. It provides new insight into
breast cancer metastasis and suggests a potential new therapeutic target for
breast cancer therapy.