Promotion of Melanoma Cell Proliferation by Cyclic Straining through Regulatory Morphogenesis

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.

Keywords: cyclic straining; cytoskeleton; mechanotransduction; melanoma; proliferation.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Cell Proliferation / genetics
  • DNA
  • Humans
  • Mechanotransduction, Cellular / physiology
  • Melanoma* / genetics
  • Melanoma, Cutaneous Malignant
  • Morphogenesis
  • Skin Neoplasms*
  • Transcription Factors / metabolism

Substances

  • Actins
  • Transcription Factors
  • DNA