Tropomodulin 1 is essential for chemotherapy sensitivity and associated with better outcome in triple-negative breast cancer.

OBJECTIVES: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC), characterized by poor clinical behaviors and outcomes. TMOD1 was reported as a downstream target of NF-κB contributing to the growth of cancer cells. However, it's impacts on TNBC patients' prognosis and treatment response remain unclear.

METHODS: The prognostic value of TMOD1 was analyzed by data from the Kaplan-Meier database and verified through immunohistochemical evaluation from 190 TNBC patients in West China Hospital (WCH). Cell Counting Kit-8 assay, Transwell cell migration assay and Matrigel invasion assay were used for in vitro study. TNBC cells treated with gradient dosage of doxorubicin (Dox), paclitaxel (PTX), and 5-fluorouracil (5-FU) for chemotherapy sensitivity assay. The chemotherapy sensitivity of Dox in vivo was further confirmed by cell line-derived xenograft (CDX) model.

RESULTS: TNBC patients with high TMOD1 expression had longer overall survival (OS) and recurrence-free survival (RFS) in both Kaplan-Meier plotter database and in cohort from WCH. In cellular functional study, overexpression of TMOD1 promoted TNBC cells' proliferation, migration and invasion. It also enhanced TNBC sensitivity to Dox treatment both in vivo and in vitro.

CONCLUSIONS: High TMOD1 expression in TNBC patients is associated with better prognosis. Although TMOD1 expression promotes TNBC cell proliferation, migration, and invasion, TMOD1 enhances the sensitivity to Dox therapy both in vivo and in vitro, which might contribute to improve the prognosis for TNBC patients.