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.

AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity

“…In this research, transwell assays showed that the inhibition of migration and invasion induced by AP4 knockdown could be abrogated by restoring LAPTM4B expression, which was consistent with the expression of epithelial–mesenchymal transition (EMT)‐related proteins on immunoblot analysis. Although a series of clinical experiments have shown that various kinds of carcinomas with LAPTM4B‐35 overexpression present more invasive characteristics, the mechanism of the effect of LAPTM4B on migration and invasion is still unclear (Xiao et al ., ). Previous researches suggested that the possible mechanism of the effect of LAPTM4B on migration and invasion was the interaction between LAPTM4B and SH3 domain‐containing proteins that are involved in many signalling pathways (Liu et al ., ).…”

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

“…LAPTM4B (the lysosome-associated protein transmembrane-4b gene) is considered as an oncogene, and its overexpression has been proven to promote the proliferation of various tumor cells, boost invasion and metastasis, resist apoptosis, initiate autophagy, and assist drug resistance. [35][36][37][38] Overexpression of LAPTM4B in breast cancer cells results in resistance to anthracycline, and its knockdown can sensitize the drug response. 39 NGFRAP1 (nerve growth factor receptor-associated protein 1) is an apoptosisrelated gene, and its expression is downregulated in some solid organ malignancies and chronic lymphocytic leukemia.…”

The Regulation and Function of the L-Type Amino Acid Transporter 1 (LAT1) in Cancer

“…The majority of these results came from studies conducted in Hela cells, and the role of LAPTM4b for mTORC1 activity was confirmed in MDA-MB-231 (breast) or HEPG2 (liver) cancer cells [17]. In addition, LAPTM4b is overexpressed in breast cancers compared with normal breast tissue, and it is more highly expressed in more advanced cancers, indicating that it is associated with breast cancer progression [19,20]. …”