Neuron specific enolase promotes tumor metastasis by activating the Wnt/β-catenin pathway in small cell lung cancer

Zhiqiang Zha; Dailing Li; Peiling Zhang; Peipei Wang; Xisheng Fang; Xia Liu; Chengyin Weng; Baoxiu Li; Yong Wu; Haibo Mao; Lina Wang; Lin Xu; Jiaming Dong; Mingmei Guan; Lin Lu; Guolong Liu

doi:10.1016/j.tranon.2021.101039

Neuron specific enolase promotes tumor metastasis by activating the Wnt/β-catenin pathway in small cell lung cancer

Transl Oncol. 2021 Apr;14(4):101039. doi: 10.1016/j.tranon.2021.101039. Epub 2021 Feb 19.

Authors

Zhiqiang Zha¹, Dailing Li¹, Peiling Zhang¹, Peipei Wang², Xisheng Fang³, Xia Liu³, Chengyin Weng³, Baoxiu Li³, Yong Wu³, Haibo Mao³, Lina Wang³, Lin Xu³, Jiaming Dong², Mingmei Guan³, Lin Lu⁴, Guolong Liu⁵

Affiliations

¹ Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China.
² Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China.
³ Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China; Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China.
⁴ Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China; Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China. Electronic address: eylinlv@scut.edu.cn.
⁵ Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China; Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China. Electronic address: eyglliu@scut.edu.cn.

Abstract

Neuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. In this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration and invasion of SCLC cells. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells. Moreover, overexpression of NSE increased the protein expression of β-catenin and its downstream target genes, and silencing β-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with β-catenin and inhibited the degradation of β-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and distant metastasis of SCLC cells in vivo. In summary, our results revealed that NSE could promote the EMT process of SCLC cells by activating the Wnt/β-catenin signaling pathway, thereby promoting cell migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.

Keywords: Epithelial-mesenchymal transition; Metastasis; Neuron-specific enolase; Small cell lung cancer; Wnt/β-catenin.