抑制细胞黏附蛋白 DPYSL3 可促进肺癌转移。

Inhibition of cell-adhesion protein DPYSL3 promotes metastasis of lung cancer.

机构信息

Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated Tongji University, 507 Zhengmin road, Shanghai, 200433, China.

Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Discipline Construction Research Center of China Hospital Development Institute, Shanghai Jiao Tong University, 639 Zhizaoju road, Shanghai, 200011, China.

出版信息

Respir Res. 2018 Mar 7;19(1):41. doi: 10.1186/s12931-018-0740-0.

BACKGROUND

Our previous screening study suggested that the cell-adhesions protein Dihydropyrimidinase-like 3 (DPYSL3) was a candidate metastatic lung cancer related molecule. This study aimed to analyze the correlation between DPYSL3 and metastatic lung cancer.

METHODS

Stable DPYSL3 knockdown Lewis lung carcinoma (LLC) cells were constructed with a retroviral system. Cell migration and invasion assays were performed to determine the role of DPYSL3 in LLC cells' migration and invasion changes. A metastatic lung tumor model in which the stable DPYSL3 knockdown LLC cells were injected through tail vein was used to analyze the role of DPYSL3 in tumor metastasis in vivo. The correlation between DPYSL3 expression and the survival time of lung cancer patients were analyzed in KMPLOT database.

RESULTS

Knockdown of DPYSL3 promoted the migratory and invasive of LLC cells compared to the control group. Meanwhile, the motility of LLC cells was also increased with the inhibition of DPYSL3. The TGFβ-induced EMT increased when DPYSL3 was inhibited. The expression of EMT markers, TWIST1 and N-cadherin, significantly increased to almost two times with the knockdown of DPYSL3. Furthermore, inhibition of DPYSL3 promoted the progression of metastatic xenograft in C57BL/6 mice. The expression level of DPYSL3 decreased in lung cancer patients with distant metastasis.

CONCLUSIONS

Knockdown of DPYSL3 promoted the metastatic ability of LLC cells in vitro and in vivo.

背景

我们之前的筛选研究表明，细胞黏附蛋白二氢嘧啶酶样 3（DPYSL3）是候选的转移性肺癌相关分子。本研究旨在分析 DPYSL3 与转移性肺癌的相关性。

方法

利用逆转录病毒系统构建稳定敲低 DPYSL3 的 Lewis 肺癌（LLC）细胞。通过细胞迁移和侵袭实验来确定 DPYSL3 在 LLC 细胞迁移和侵袭变化中的作用。通过尾静脉注射稳定敲低 DPYSL3 的 LLC 细胞构建转移性肺癌肿瘤模型，分析 DPYSL3 在体内肿瘤转移中的作用。在 KMPLOT 数据库中分析 DPYSL3 表达与肺癌患者生存时间的相关性。

结果

与对照组相比，敲低 DPYSL3 促进了 LLC 细胞的迁移和侵袭。同时，随着 DPYSL3 的抑制， LLC 细胞的运动性也增加了。TGFβ 诱导的 EMT 增加，当 DPYSL3 被抑制时。EMT 标志物 TWIST1 和 N-钙黏蛋白的表达显著增加，几乎是敲低 DPYSL3 的两倍。此外，抑制 DPYSL3 促进了 C57BL/6 小鼠转移性异种移植的进展。在有远处转移的肺癌患者中，DPYSL3 的表达水平降低。