HNMT promotes the motility-associated structures of breast cancer cells through the PI3K/Akt signaling pathway to promote tumor progression.

[BACKGROUND] Breast cancer (BC) is a tumor type that severely threatens the health and lives of women worldwide. Cancer cell motility often leads to the distant metastasis of BC. Histamine N-methyltransferase (HNMT) has been reported to be associated with poor prognosis in patients with BC; however, its role in BC cell motility remains unclear. Therefore, this study aimed to investigate the role of HNMT in BC cell motility.

[METHODS] MDA-MB-231 cells were injected into the mammary fat pads of female BALB/c nude mice to establish a BC orthotopic tumor model, and BC lung metastasis was evaluated via HE staining. To investigate the effects of HNMT on the malignant behavior of BC cells, HNMT was knocked down or overexpressed in MDA-MB-231 cells. Cell proliferation, migration and invasion were analyzed by using CCK-8, scratch and Transwell assays, respectively. Moreover, the expression of key genes and proteins was detected via RT-qPCR, Western blotting, immunofluorescence and immunohistochemistry; additionally, the formation of invasive pseudopodia was detected via phalloidin staining.

[RESULTS] HNMT expression was upregulated in BC. HNMT knockdown inhibited BC growth and lung metastasis in vivo. In vitro, HNMT knockdown inhibited MDA-MB-231 cell proliferation, migration, and invasion, as well as the formation of invasive pseudopodia and epithelial-mesenchymal transition (EMT), whereas the overexpression of HNMT exhibited the opposite effect, thus indicating that the upregulation of HNMT expression is associated with BC cell motility. In addition, HNMT was observed to activate the PI3K/AKT pathway. Treatment with the PI3K activator 740 Y-P alleviated the inhibitory effect of HNMT knockdown on the proliferation, migration, invasion, and EMT of MDA-MB-231 cells.

[CONCLUSION] HNMT promoted BC cell invasion and metastasis through the activation of the PI3K/AKT signaling pathway, thereby promoting the malignant progression and lung tumor metastasis of BC. This study provides novel insights and potential therapeutic strategies for BC treatment.