BTB domain-containing 7 predicts low recurrence and suppresses tumor progression by deactivating Notch1 signaling in breast cancer.

ABSTRACT

PURPOSE: BTB domain-containing 7 (BTBD7) has been found to regulate epithelial tissue remodeling and branched organ formation and has been reported to modulate the biological behavior of several cancers. However, its role in breast cancer has not been identified. This study investigated the biological role and prognostic value of BTBD7 in breast cancer. METHODS: We identified the BTBD7 expression pattern using the GENT2 database and assessed its expression in breast cancer tissue and cell lines using quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry. We conducted a clinical relevance and survival analysis on a cohort of 121 breast cancer cases from our follow-up and validated it in a Kaplan-Meier plotter. The gain-loss effect of BTBD7 on cell proliferation, invasion, and migration was detected in vitro. We employed a xenograft mouse metastatic model for in vivo validation and performed a Cignal Finder Cancer 10-Pathway Reporter Array, western blot, immunofluorescence, Cell Counting Kit-8, and transwell invasion/migration assays to analyze the potential mechanism. RESULTS: BTBD7 was downregulated in human breast cancer cell lines and tissues. Decreased BTBD7 expression correlated with a positive lymph node status, lymphovascular invasion, and TNM stage, while high BTBD7 expression correlated with low breast cancer recurrence. BTBD7 suppressed cell proliferation, invasion/migration, and tumor metastasis in breast cancer. The mechanism studied suggested that the inhibitory role of BTBD7 was through the deactivation of Notch1 signaling in breast cancer. CONCLUSION: BTBD7 suppresses tumor progression, and its high expression correlates with low recurrence in breast cancer.