LAPTM4B Predicts Axillary Lymph Node Metastasis in Breast Cancer and Promotes Breast Cancer Cell Aggressiveness in Vitro

Abstract

Purpose: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is associated with the prognosis of several human malignancies. In this study, the role of LAPTM4B in the metastatic potential of breast cancer (BC) and its underlying molecular mechanisms were investigated. Methods: The relationship between LAPTM4B expression and axillary lymph node metastasis was determined in 291 BC specimens by immunohistochemistry. The expression of LAPTM4B in paired BC cells was overexpressed and inhibited to analyse the role of LAPTM4B in the aggressiveness of BC. Cell proliferation, migration and invasion were assessed in vitro. Metastasis-related protein levels were detected through Western blot. Results: Immunohistochemical staining demonstrated that high expression level of LAPTM4B was independently associated with axillary lymph node metastasis (odds ratio=2.428; 95%CI=1.333- 4.425; P=0.004). The LAPTM4B inhibition in MCF-7 cells inhibited cell proliferation, migration, invasion, and resulted in simultaneous downregulation of phosphorylated N-cadherin, vimentin, and upregulation of E-cadherin. By contrast, the LAPTM4B overexpression promoted cell proliferation, migration, invasion, and led to simultaneous upregulation of N-cadherin, vimentin, and downregulation of E-cadherin in T47D cells. Conclusions: High expression level of LAPTM4B predicts tumor metastatic potential in patients with BC. Our results provide the first evidence of the role of LAPTM4B as an Epithelial-mesenchymal transition (EMT) inducer that promotes aggressiveness in BC cells.