Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China.
Oncol Rep. 2023 Mar;49(3). doi: 10.3892/or.2023.8497. Epub 2023 Feb 17.
Breast cancer remains the most common malignancy and the leading cause of cancer‑associated mortality in women worldwide. Lysosomal protein transmembrane 5 (LAPTM5), a lysosomal membrane protein, plays an important role in several human malignancies. However, the biological functions and mechanism of LAPTM5 in breast cancer remain unclear. In the present study, the potential tumor‑promoting effect of LAPTM5 was predicted by bioinformatics analysis. LAPTM5 was highly expressed in breast cancer clinical specimens. Moreover, studies demonstrated that cell proliferation, migration and invasion, as well as the process of epithelial‑mesenchymal transition (EMT) were promoted by LAPTM5 overexpression and were suppressed by LAPTM5 downregulation . The tumor‑promoting effects of LAPTM5 were also confirmed by xenograft tumor assay . It was found that the tumor‑promoting effects of LAPTM5 were partly dependent on the activation of the Wnt/β‑catenin signaling pathway. Furthermore, dual‑luciferase and chromatin immunoprecipitation assays verified that the transcription factor forkhead box protein 3 (FOXP3) directly bound to the promoter of LAPTM5 and negatively regulated its expression. Taken together, the present findings indicated that LAPTM5, negatively regulated by FOXP3, promoted the malignant phenotypes of breast cancer through activating the Wnt/β‑catenin signaling pathway.
乳腺癌仍然是全球范围内最常见的恶性肿瘤，也是癌症相关死亡的主要原因。溶酶体蛋白跨膜 5（LAPTM5）是一种溶酶体膜蛋白，在多种人类恶性肿瘤中发挥重要作用。然而，LAPTM5 在乳腺癌中的生物学功能和机制尚不清楚。在本研究中，通过生物信息学分析预测了 LAPTM5 的潜在促瘤作用。LAPTM5 在乳腺癌临床标本中高表达。此外，研究表明，LAPTM5 过表达促进细胞增殖、迁移和侵袭，以及上皮-间充质转化（EMT）过程，而 LAPTM5 下调则抑制这些过程。LAPTM5 的促瘤作用也通过异种移植肿瘤实验得到了证实。结果发现，LAPTM5 的促瘤作用部分依赖于 Wnt/β-catenin 信号通路的激活。此外，双荧光素酶和染色质免疫沉淀实验验证了转录因子叉头框蛋白 3（FOXP3）直接结合 LAPTM5 的启动子并负调控其表达。综上所述，这些发现表明，FOXP3 负调控的 LAPTM5 通过激活 Wnt/β-catenin 信号通路促进乳腺癌的恶性表型。
