| First Author | Nagumo Y | Year | 2021 |
| Journal | Cancer Lett | Volume | 511 |
| Pages | 15-25 | PubMed ID | 33945837 |
| Mgi Jnum | J:306530 | Mgi Id | MGI:6715774 |
| Doi | 10.1016/j.canlet.2021.04.014 | Citation | Nagumo Y, et al. (2021) PLD1 promotes tumor invasion by regulation of MMP-13 expression via NF-kappaB signaling in bladder cancer. Cancer Lett 511:15-25 |
| abstractText | Invasion of bladder cancer (BC) cells from the mucosa into the muscle layer is canonical for BC progression while phospholipase D isoform 1 (PLD1) is known to mediate development of cancer through phosphatidic acid (PA) production. We therefore used in silico, in vitro and in vivo approaches to detail the effect of PLD1 on BC invasion. In BC patients, higher levels of PLD1 expression were associated with poor prognoses. PLD1 knockdown significantly suppressed cellular invasion by human BC cells and matrix metalloproteinase-13 (MMP-13) was observed to mediate this effect. In our mouse bladder carcinogenesis model, the development of invasive BCs was suppressed by PLD1 knockout and a global transcriptomic analysis in this model indicated MMP-13 as a potential tumor invasion gene with NF-kappaB (nuclear factor-kB) as its transcriptional regulator. Furthermore, PA administration increased MMP-13 expression in line with NF-kappaB p65 phosphorylation levels. Collectively, we demonstrate that PLD1 promotes tumor invasion of BC by regulation of MMP-13 expression through the NF-kappaB signaling pathway and that PLD1 might be a potential therapeutic target to prevent clinical progression in BC patients. |
