Department of Biomedical Engineering, Yale University, New Haven, CT 06511.
Yale Cancer Center, Yale University, New Haven, CT 06511.
Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2220062120. doi: 10.1073/pnas.2220062120. Epub 2023 Sep 18.
Physical forces are prominent during tumor progression. However, it is still unclear how they impact and drive the diverse phenotypes found in cancer. Here, we apply an integrative approach to investigate the impact of compression on melanoma cells. We apply bioinformatics to screen for the most significant compression-induced transcriptomic changes and investigate phenotypic responses. We show that compression-induced transcriptomic changes are associated with both improvement and worsening of patient prognoses. Phenotypically, volumetric compression inhibits cell proliferation and cell migration. It also induces organelle stress and intracellular oxidative stress and increases pigmentation in malignant melanoma cells and normal human melanocytes. Finally, cells that have undergone compression become more resistant to cisplatin treatment. Our findings indicate that volumetric compression is a double-edged sword for melanoma progression and drives tumor evolution.
物理力在肿瘤进展中起着重要作用。然而，目前尚不清楚它们如何影响和驱动癌症中发现的不同表型。在这里，我们应用一种综合的方法来研究压缩对黑色素瘤细胞的影响。我们应用生物信息学筛选出最显著的压缩诱导的转录组变化，并研究表型反应。我们表明，压缩诱导的转录组变化与改善和恶化患者预后都有关。表型上，体积压缩抑制细胞增殖和细胞迁移。它还诱导细胞器应激和细胞内氧化应激，并增加恶性黑色素瘤细胞和正常人黑素细胞的色素沉着。最后，经历过压缩的细胞对顺铂治疗更有抵抗力。我们的研究结果表明，体积压缩对黑色素瘤的进展是一把双刃剑，推动了肿瘤的进化。
