脂质运载蛋白2通过一种新的正反馈回路促进食管鳞状细胞癌细胞的迁移和侵袭。

Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop.

作者信息

Du Ze-Peng, Wu Bing-Li, Xie Yang-Min, Zhang Ying-Li, Liao Lian-Di, Zhou Fei, Xie Jian-Jun, Zeng Fa-Min, Xu Xiu-E, Fang Wang-Kai, Li En-Min, Xu Li-Yan

机构信息

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China; Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, Guangdong Province 515041, China.

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.

出版信息

Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2240-50. doi: 10.1016/j.bbamcr.2015.07.007. Epub 2015 Jul 17.

DOI:10.1016/j.bbamcr.2015.07.007

PMID:26190820

Abstract

Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.

摘要

脂质运载蛋白2（LCN2）是食管鳞状细胞癌（ESCC）的一个不良预后因素，然而其功能作用和分子作用机制仍有待阐明。在此，我们描述了LCN2在ESCC中的功能和信号通路。ESCC细胞中LCN2的过表达在体外加速了细胞迁移和侵袭，并在体内促进了肺转移。阻断LCN2表达可抑制其促癌作用。LCN2的过表达或用重组人LCN2蛋白处理均可增强MEK/ERK通路的激活，进而增加内源性LCN2以提高MMP-9活性。由pERK1/2诱导的p-丝切蛋白减少和p-ERM增加导致细胞骨架F-肌动蛋白重排，并改变由LCN2介导的ESCC细胞行为。因此，MMP-9的激活和F-肌动蛋白的重排揭示了LCN2在ESCC中的作用机制。这些结果表明，LCN2通过一个新的正反馈环促进ESCC细胞的迁移和侵袭。