Seehawer Marco, Polyak Kornelia
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Trends Cell Biol. 2025 Mar 14. doi: 10.1016/j.tcb.2025.02.010.
Metalloproteinases (MPs) are crucial for development and homeostasis due to their diverse physiological functions, from the cellular to the organismal level. Their activity is tightly regulated at multiple levels, including epigenetic regulation through DNA methylation and histone modifications. Aberrant MP expression can result in pathological events, involving extracellular matrix remodeling, which can facilitate cancer cell invasion and dissemination. As clinical testing of MP inhibitors has been limited by toxicity, alternative approaches are needed. Epigenetically-driven MP expression is often specific to cancer cells, giving an enticing possibility for cancer cell-specific targeting. Moreover, aberrant epigenetic activity can also drive other metastatic events. Therefore, targeting the epigenetic regulators of MP expression may be a promising alternative approach for the prevention and treatment of metastatic disease.
金属蛋白酶（MPs）因其从细胞水平到机体水平的多种生理功能，对发育和内环境稳态至关重要。它们的活性在多个层面受到严格调控，包括通过DNA甲基化和组蛋白修饰的表观遗传调控。MP异常表达可导致病理事件，包括细胞外基质重塑，这可促进癌细胞的侵袭和扩散。由于MP抑制剂的临床试验受到毒性限制，需要其他替代方法。表观遗传驱动的MP表达通常对癌细胞具有特异性，为癌细胞特异性靶向提供了诱人的可能性。此外，异常的表观遗传活性也可驱动其他转移事件。因此，靶向MP表达的表观遗传调节因子可能是预防和治疗转移性疾病的一种有前景的替代方法。
