期刊
TRANSLATIONAL ONCOLOGY
卷 17, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2021.101335
关键词
SNF5; Matrix stiffness; Melanoma; Immune escape
类别
资金
- National Natural Science Foundation of Chongqing [cstc2021ycjh-bgzxm0169]
- National Natural Science Foundation of China [31670952]
This study found that increased stiffness of the extracellular matrix promotes proliferation, epithelial-mesenchymal transition (EMT), and immune escape of melanoma cells. SNF5 was identified as a key mediator in these processes.
Increased stiffness of the extracellular matrix is an important hallmark of melanoma development and progression, but its regulatory role and related mechanisms remain unclear. We adapted polydimethylsiloxane (PDMS)-micropillar-based matrix platform and investigated the effect of matrix stiffness on the proliferation, epithelial-mesenchymal transition (EMT), and immune escape of melanoma cells. We observed a stiff matrix enhanced cell proliferation, EMT, and immune escape of A375 cells. Furthermore, the expression of SNF5 on the stiffer matrix was higher than that on the softer matrix. Next, we investigated whether SNF5 is an important transducer in response to matrix stiffness. Our results revealed that knockdown of SNF5 significantly decreased stiff matrix-induced activation of cell proliferation, EMT and immune escape. Meanwhile, the overexpression of SNF5 showed its ability to increase cell proliferation, invasion and immune escape by activating the STAT-3 pathway in vitro. Furthermore, SNF5 deficiency elevated the level of tumor-infiltrating CD8(+)T cells and decreased the number of PD-L1 positive cells in vivo. Together, our findings suggested that stiffer substrate enhanced melanoma development by upregulating SNF5 expression, and SNF5 is a key mediator of stiffer matrixinduced immune evasion of melanoma cancer cells.
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