Filamin A Is a Potential Driver of Breast Cancer Metastasis via Regulation of MMP-1

Abstract

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.

Spatial transcriptomic interrogation of the tumour-stroma boundary in a 3D engineered model of ameloblastoma

“…5 C). The matrix remodelling gene Filamin A (FLNA) [ 29 ], was significantly upregulated where a bone stroma was present compared to an acellular stroma (p < 0.05) ( Fig. 5 F).…”

Spatial transcriptome profiling ofin vitro3D tumouroids to study tumour-stroma interactions

“…Among matrix remodelling targets, the expression of collagen genes such as collagen type 3 Alpha 2 Chain (COL3A1) and COL6A3 in AM-1 cultured with HGF stroma were higher compared to acellular and hOB stroma (Figure 6C) . The matrix remodelling gene Filamin A (FLNA) (26), was significantly upregulated with hOB stroma compared to acellular stroma (p<0.05) (Figure 5F) .…”

Role of Filamin A in Growth and Migration of Breast Cancer—Review

“…There are numerous reports on the role of FLNa in cells' migration and invasiveness. Most researchers concluded that overexpression of FLNa contributes to increased motility and invasive properties of breast cancer cells [8,42,46,47]. Shao et al noted the duality of FLNa's role in the metastasis of breast cancer [8].…”