HOX genes and tumor metastasis: epigenetic regulatory mechanisms

Tumor metastasis, a defining feature of malignant tumors, entails the dissemination of tumor cells from the primary site to distant anatomical locations via multiple pathways such as the circulatory or lymphatic systems, or through direct invasion‑leading to the formation of secondary tumor foci. This complex process encompasses a series of biological mechanisms, including cell adhesion, migration, invasion, and subsequent proliferation and survival at the new site. Transcription factors play a critical role in regulating gene expression and significantly influence tumor metastasis. Previous studies have demonstrated that HOX genes, which act as transcription factors, modulate the expression of downstream targets involved in metastatic progression via specific epigenetic pathways. Furthermore, they activate relevant signaling pathways to promote tumor invasion and migration. This review systematically analyzes the three primary epigenetic pathways through which HOX genes exert their regulatory functions: nucleic acid modification, histone modification, and RNA interference. We also discuss potential therapeutic strategies targeting these mechanisms and address current challenges in the field.