Twardak Damian, Havryliuk Vita, Gagat Maciej
Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-092 Bydgoszcz, Poland.
Department of Morphological and Physiological Sciences, Faculty of Medicine, Collegium Medicum, Mazovian Academy in Płock, 09-402 Pock, Poland.
Int J Mol Sci. 2025 Aug 13;26(16):7829. doi: 10.3390/ijms26167829.
Cutaneous malignant melanoma remains one of the most aggressive forms of skin cancer, characterized by high metastatic potential and resistance to standard therapies. Emerging evidence suggests that transient receptor potential (TRP) channels, non-selective cation channels involved in calcium homeostasis, and cellular stress responses play a pivotal role in melanoma development and progression. This review highlights the physiological expression of key TRP subfamilies (TRPM1, TRPM7, TRPM8, TRPV1, TRPV4, and TRPM2) in melanocytes and discusses their dysregulation in melanoma cells. TRPM1 is implicated as a tumor suppressor, whereas TRPM7, TRPV1, and TRPV4 often function as both melanoma suppressor or oncogenic drivers, modulating proliferation, apoptosis, and metastasis. TRPM2, which is responsive to oxidative stress, supports melanoma cell survival under metabolic stress. The potential of TRP channels as diagnostic biomarkers and therapeutic targets is evaluated, with attention paid to current pharmacological approaches and research challenges. The complexity and context-dependency of TRP function in melanoma underscore the need for isoform-specific modulation and personalized therapeutic strategies.
皮肤恶性黑色素瘤仍然是最具侵袭性的皮肤癌形式之一,其特征是具有高转移潜能且对标准疗法耐药。新出现的证据表明,瞬时受体电位(TRP)通道,即参与钙稳态和细胞应激反应的非选择性阳离子通道,在黑色素瘤的发生和发展中起关键作用。本综述重点介绍了关键TRP亚家族(TRPM1、TRPM7、TRPM8、TRPV1、TRPV4和TRPM2)在黑素细胞中的生理表达,并讨论了它们在黑色素瘤细胞中的失调情况。TRPM1被认为是一种肿瘤抑制因子,而TRPM7、TRPV1和TRPV4通常既作为黑色素瘤抑制因子又作为致癌驱动因子,调节增殖、凋亡和转移。对氧化应激有反应的TRPM2在代谢应激下支持黑色素瘤细胞存活。评估了TRP通道作为诊断生物标志物和治疗靶点的潜力,同时关注了当前的药理学方法和研究挑战。TRP功能在黑色素瘤中的复杂性和背景依赖性强调了对异构体特异性调节和个性化治疗策略的需求。