1. EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.
- Author
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Chen CH, Chen Y, Li YN, Zhang H, Huang X, Li YY, Li ZY, Han JX, Wu XY, Liu HJ, and Sun T
- Subjects
- Animals, Humans, Mice, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Disease Progression, Cell Differentiation, Early Growth Response Protein 3 genetics, Early Growth Response Protein 3 metabolism, Melanoma metabolism, Melanoma pathology, Melanoma genetics, Schwann Cells metabolism
- Abstract
The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
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