Department of Immunology, School of Medicine, Nankai University.
Institute of Disaster Medicine, Tianjin University, Tianjin, China.
Anticancer Drugs. 2021 Jun 1;32(6):626-634. doi: 10.1097/CAD.0000000000001036.
Caveolin-1 (CAV-1) can extensively regulate lipid transportation, cell growth and cell death. In the present study, we revealed a novel function of CAV-1 in inhibiting glycosylation of other molecules in murine breast cancer cell line. After the silencing of CAV-1, we found that the mRNA and protein expressions of cluster of differentiation 147 (CD147) and its related molecules (MCT4, matrix metalloproteinase MMP2 and MMP9) increased in the breast cancer cells. Meanwhile, the migration and invasion of the breast cancer cells were significantly enhanced assessed by cell wound healing experiment and transwell assays. Further, the gelatin zymography and lactate assay in the cells also showed the strengthened enzyme activity of MMP9 and the increased extracellular lactate concentration, respectively, after the silencing of CAV-1. Notably, the glycosylation level of CD147 overtly increased after the inhibition of CAV-1 detected by Western Blot analysis, whereas upregulation of CAV-1 did the opposite. Therefore, the findings suggest that the downregulation of CAV-1 can promote breast cancer cell progression probably by highly glycosylated CD147.
窖蛋白-1（CAV-1）可以广泛调节脂质运输、细胞生长和细胞死亡。在本研究中，我们揭示了 CAV-1 在抑制鼠乳腺癌细胞系中其他分子糖基化方面的新功能。沉默 CAV-1 后，我们发现乳腺癌细胞中 CD147 及其相关分子（MCT4、基质金属蛋白酶 MMP2 和 MMP9）的 mRNA 和蛋白表达增加。同时，通过细胞划痕实验和 Transwell 分析评估，乳腺癌细胞的迁移和侵袭能力明显增强。此外，细胞中的明胶酶谱和乳酸测定也分别显示，沉默 CAV-1 后 MMP9 的酶活性增强，细胞外乳酸浓度增加。值得注意的是，Western Blot 分析显示，CAV-1 抑制后 CD147 的糖基化水平明显增加，而上调 CAV-1 则相反。因此，研究结果表明，CAV-1 的下调可能通过高度糖基化的 CD147 促进乳腺癌细胞的进展。
