Lipocalin 2 negatively regulates cell proliferation and epithelial to mesenchymal transition through changing metabolic gene expression in colorectal cancer.
Lipocalin 2 negatively regulates cell proliferation and epithelial to mesenchymal transition through changing metabolic gene expression in colorectal cancer.
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DOI：
10.1111/cas.13389
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发表时间：
2017-11
期刊：
影响因子：
5.7
通讯作者：
Kim SW
中科院分区：
文献类型：
--
作者：
Kim SL;Lee ST;Min IS;Park YR;Lee JH;Kim DG;Kim SW
脂质运载蛋白2（LCN2）是脂质运载蛋白超家族的成员，在多种癌症的发生和进展中发挥重要作用。然而，LCN2在结直肠癌（CRC）中的表达模式和功能作用仍知之甚少。本研究的目的是探讨LCN2是否与CRC中的增殖和上皮 - 间质转化（EMT）相关，并阐明潜在的信号通路。与正常组织相比，LCN2在CRC细胞中优先表达。然而，转移性或晚期CRC中的LCN2表达明显低于非转移性或早期CRC。在高表达LCN2的CRC细胞中使用小干扰RNA（siRNA）敲低LCN2可诱导细胞增殖以及从上皮状态到间质状态的形态转变。此外，CRC细胞中LCN2的下调增加了细胞迁移和侵袭，这涉及EMT标志物的调节。敲低LCN2还诱导了葡萄糖消耗和乳酸产生，同时伴有能量代谢相关基因的增加。综上所述，我们的研究结果表明LCN2对CRC细胞的增殖、EMT和能量代谢具有负向调节作用。因此，LCN2可能是CRC中的一种候选转移抑制因子和潜在治疗靶点。
Lipocalin 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the expression pattern and functional role of LCN2 in colorectal cancer (CRC) is still poorly understood. The purpose of the present study was to investigate whether LCN2 is associated with proliferation and the epithelial–mesenchymal transition (EMT) in CRC and to elucidate the underlying signaling pathways. LCN2 was preferentially expressed in CRC cells compared to normal tissues. However, LCN2 expression was significantly lower in metastatic or advanced‐stage CRC than in non‐metastatic or early stage CRC. Knockdown of LCN2 using small interfering RNA (siRNA) in CRC cells expressing a high level of LCN2 induced cell proliferation and a morphological switch from an epithelial to mesenchymal state. Furthermore, downregulation of LCN2 in CRC cells increased cell migration and invasion involved in the regulation of EMT markers. Knockdown of LCN2 also induced glucose consumption and lactate production, accompanied by an increase in energy metabolism‐related genes. Taken together, our findings indicated that LCN2 negatively modulated proliferation, EMT and energy metabolism in CRC cells. Accordingly, LCN2 may be a candidate metastasis suppressor and potential therapeutic target in CRC.
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