Maiques Oscar, Sanz-Moreno Victoria
Barts Cancer Institute, John Vane Science Building, Queen Mary University of London, London, UK.
Exp Dermatol. 2022 Jan;31(1):82-88. doi: 10.1111/exd.14423. Epub 2021 Jul 5.
Abnormal cell migration and invasion underlie metastatic dissemination, one of the major challenges for cancer treatment. Melanoma is one of the deadliest and most aggressive forms of skin cancer due in part to its migratory and metastatic potential. Cancer cells use a variety of migratory strategies regulated by cytoskeletal remodelling. In particular, we discuss the importance of amoeboid invasive melanoma strategies, since they have been identified at the edge of human melanomas. We hypothesize that the presence of amoeboid melanoma cells will favour tumor progression since they are invasive and metastatic; they support immunosuppression; they harbour cancer stem cell properties and they are involved in therapy resistance. The Rho-ROCK-Myosin II pathway is key to maintain amoeboid melanoma invasion but this pathway is further regulated by pro-tumorigenic/pro-metastatic/pro-survival signalling pathways such as JAK-STAT3, TGFβ-SMAD, NF-κB, Wnt11/5-FDZ7 and BRAF -MEK-ERK. These pathways support amoeboid behaviour and are actionable in the clinic. After melanoma wide surgical margin removal, we propose that possible remaining melanoma cells should be eradicated using anti-amoeboid therapies.
异常的细胞迁移和侵袭是转移性扩散的基础，而转移性扩散是癌症治疗的主要挑战之一。黑色素瘤是最致命、最具侵袭性的皮肤癌形式之一，部分原因在于其迁移和转移潜能。癌细胞采用多种受细胞骨架重塑调节的迁移策略。特别地，我们讨论了阿米巴样侵袭性黑色素瘤策略的重要性，因为它们已在人类黑色素瘤边缘被发现。我们假设阿米巴样黑色素瘤细胞的存在将有利于肿瘤进展，因为它们具有侵袭性和转移性；它们支持免疫抑制；它们具有癌症干细胞特性并且它们与治疗抗性有关。Rho-ROCK-肌球蛋白II途径是维持阿米巴样黑色素瘤侵袭的关键，但该途径进一步受促肿瘤发生/促转移/促生存信号通路如JAK-STAT3、TGFβ-SMAD、NF-κB、Wnt11/5-FDZ7和BRAF -MEK-ERK的调节。这些途径支持阿米巴样行为并且在临床上是可操作的。在黑色素瘤进行广泛的手术切缘切除后，我们建议应使用抗阿米巴样疗法根除可能残留的黑色素瘤细胞。
