期刊
CANCER LETTERS
卷 479, 期 -, 页码 100-111出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.03.014
关键词
LAMP3; VASP; PKA; Metastasis; Esophageal cancer
类别
资金
- National Key R&D Program of China [2016YFC1302100]
- CAMS Innovation Fund for Medical Sciences [2016-I2M-1-001, 2019-I2M-1-003]
Metastasis is still a major cause of cancer-related mortality. Lysosome-associated membrane protein 3 (LAMP3) has been implicated in the invasiveness and metastasis of multiple cancer types; however, the underlying mechanisms are unclear. In this study, we found that LAMP3 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and that this increased expression positively correlated with lymph node metastasis. Depletion of LAMP3 dramatically suppressed the motility of ESCC cells in vitro and experimental pulmonary and lymph node metastasis in vivo. Importantly, knockdown of LAMP3 increased the level of phosphorylated VASP (Ser239), which attenuated the invasive and metastatic capability of ESCC cells. We identified that cAMP-dependent protein kinase A (PKA) was responsible for the phosphorylation of VASP at Ser239. Consistently, silencing of PKA regulatory subunits diminished Ser239 phosphorylation on VASP and restored the motility capacity of LAMP3-depleted ESCC cells. In conclusion, we uncovered a previously unknown role of LAMP3 in promoting cellular motility and metastasis in ESCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据