Department of Cell Biology, Charles University, Viničná 7, 128 44 Prague, Czech Republic.
Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Průmyslová 595, 252 42 Vestec u Prahy, Czech Republic.
Biomolecules. 2021 Mar 17;11(3):449. doi: 10.3390/biom11030449.
Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid-mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.
黑色素瘤表型可塑性是肿瘤扩散和对治疗产生抵抗的基础，但它的调控机制尚不完全清楚。在体内，肿瘤微环境决定了更分化、增殖表型和去分化、侵袭表型之间的转换。我们发现，用两种结构上不相关的 p38 MAPK 抑制剂 SB2021920 和 BIRB796 处理部分去分化、侵袭性的 A375M2 细胞，会在 3D 胶原中诱导表型转换，这一点可以通过黑色素细胞分化标记物的表达增加和侵袭性表型标记物的丢失来证明。这种表型伴随着与阿米巴样-间充质转化相对应的形态变化。我们使用 Illumina HiSeq 平台进行 RNA 测序，以充分描述导致这种转换的转录组变化。通过与 RT-qPCR 进行比较，验证了 RNA-seq 获得的基因表达结果。本研究产生的转录组数据将扩展我们对黑色素瘤表型可塑性及其对侵袭和转移的贡献的现有认识。
