Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK.
Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK.
Nat Commun. 2020 Oct 20;11(1):5315. doi: 10.1038/s41467-020-18951-2.
Melanoma is a highly aggressive tumour that can metastasize very early in disease progression. Notably, melanoma can disseminate using amoeboid invasive strategies. We show here that high Myosin II activity, high levels of ki-67 and high tumour-initiating abilities are characteristic of invasive amoeboid melanoma cells. Mechanistically, we find that WNT11-FZD7-DAAM1 activates Rho-ROCK1/2-Myosin II and plays a crucial role in regulating tumour-initiating potential, local invasion and distant metastasis formation. Importantly, amoeboid melanoma cells express both proliferative and invasive gene signatures. As such, invasive fronts of human and mouse melanomas are enriched in amoeboid cells that are also ki-67 positive. This pattern is further enhanced in metastatic lesions. We propose eradication of amoeboid melanoma cells after surgical removal as a therapeutic strategy.
黑色素瘤是一种高度侵袭性的肿瘤，在疾病进展的早期就可能转移。值得注意的是，黑色素瘤可以通过变形虫样浸润策略进行扩散。我们在这里表明，高肌球蛋白 II 活性、高 ki-67 水平和高肿瘤起始能力是侵袭性变形虫样黑色素瘤细胞的特征。从机制上讲，我们发现 WNT11-FZD7-DAAM1 激活 Rho-ROCK1/2-肌球蛋白 II，在调节肿瘤起始潜能、局部浸润和远处转移形成中发挥关键作用。重要的是，变形虫样黑色素瘤细胞表达增殖和浸润基因特征。因此，人类和小鼠黑色素瘤的侵袭前沿富含变形虫样细胞，这些细胞也呈 ki-67 阳性。这种模式在转移性病变中进一步增强。我们提出在手术切除后消灭变形虫样黑色素瘤细胞作为一种治疗策略。
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