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通过调控形态发生进行周期性应变促进黑素瘤细胞增殖。

Promotion of Melanoma Cell Proliferation by Cyclic Straining through Regulatory Morphogenesis.

机构信息

Materials Institute of Atomic and Molecular Science, Shaanxi University of Science and Technology, Xi'an 710026, China.

School of Electro-Mechanical Engineering, Xidian University, Xi'an 710071, China.

出版信息

Int J Mol Sci. 2022 Oct 6;23(19):11884. doi: 10.3390/ijms231911884.

Abstract

The genotype and phenotype of acral melanoma are obviously different from UV-radiation-induced melanoma. Based on the clinical data, mechanical stimulation is believed to be a potential cause of acral melanoma. In this case, it is desirable to clarify the role of mechanical stimulation in the progression of acral melanoma. However, the pathological process of cyclic straining that stimulates acral melanoma is still unclear. In this study, the influence of cyclic straining on melanoma cell proliferation was analyzed by using a specifically designed cell culture system. In the results, cyclic straining could promote melanoma cell proliferation but was inefficient after the disruption of cytoskeleton organization. Therefore, the mechanotransduction mechanism of promoted proliferation was explored. Both myosin and actin polymerization were demonstrated to be related to cyclic straining and further influenced the morphogenesis of melanoma cells. Additionally, the activation of mechanosensing transcription factor YAP was related to regulatory morphogenesis. Furthermore, expression levels of melanoma-involved genes were regulated by cyclic straining and, finally, accelerated DNA synthesis. The results of this study will provide supplementary information for the understanding of acral melanoma.

摘要

肢端黑色素瘤的基因型和表型明显不同于 UV 辐射诱导的黑色素瘤。基于临床数据,机械刺激被认为是肢端黑色素瘤的潜在原因。在这种情况下,阐明机械刺激在肢端黑色素瘤进展中的作用是很有必要的。然而,刺激肢端黑色素瘤的周期性应变的病理过程尚不清楚。在这项研究中,使用专门设计的细胞培养系统分析了周期性应变对黑色素瘤细胞增殖的影响。结果表明,周期性应变可以促进黑色素瘤细胞的增殖,但在破坏细胞骨架组织后效率不高。因此,探讨了促进增殖的力传递机制。肌球蛋白和肌动蛋白聚合都与周期性应变有关,并进一步影响黑色素瘤细胞的形态发生。此外,机械敏感转录因子 YAP 的激活与调节形态发生有关。此外,黑色素瘤相关基因的表达水平受周期性应变调节,最终加速了 DNA 合成。本研究的结果将为理解肢端黑色素瘤提供补充信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7c/9569601/b0b19db3ac4a/ijms-23-11884-g001.jpg

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