MEX3A Drives Triple-Negative Breast Cancer Migration, Invasion, and Metastasis by Interacting with NTRK1

Abstract

Background: Triple-negative breast cancer (TNBC) stands out as the most aggressive form of breast cancer due to its significant propensity for metastasis. Exploring the molecular mechanisms of TNBC metastasis is essential to develop TNBC therapeutic strategies. Mex-3 RNA Binding Family Member A (MEX3A) has been recognized to promote TNBC proliferation. However, its role in TNBC metastasis hasnt been investigated. Methods: We investigated MEX3A levels in breast cancer cells, normal mammary tissues, and breast cancer tissues using Western blot analysis. Moreover, immunohistochemistry (IHC) analysis was used to determine MEX3A levels in TNBC tissues. Cell migration and invasion assays and lung metastasis assay were performed to investigate the role of MEX3A in TNBC metastasis in vitro and in vivo. Additionally, Co-immunoprecipitation was used to determine the interacting proteins of MEX3A. Results: MEX3A was upregulated in TNBC tissues compared to the normal mammary tissues, especially in TNBC tissues. Patients with high MEX3A expression exhibited shorter overall survival, distant metastasis-free-, relapse-free-, and post-progression survival time than those with low MEX3A expression (p < 0.05). MEX3A knockdown inhibited TNBC cell migration and invasion in vitro (p < 0.05). MEX3A overexpression promoted TNBC metastasis in vivo (p < 0.05). Mechanistically, MEX3A could interact with Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), resulting in activation of Ras GTPase (Ras-GTP), AKT Serine/Threonine Kinase (AKT), and Extracellular signal-regulated kinase (ERK) pathways, thereby promoting TNBC metastasis. Additionally, Ras pathway inhibitor MCP110 reversed the effect of MEX3A overexpression on TNBC cell migration and invasion. Conclusion: MEX3A is upregulated in TNBC tissues and can serve as an independent prognostic factor for TNBC patients. MEX3A promotes TNBC cell migration, invasion, and metastasis by interacting with NTRK1, resulting in the activation of Ras, AKT, and ERK pathways. These findings offer a potential therapeutic target for patients with TNBC.