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Neuron-specific enolase promotes stem cell-like characteristics of small-cell lung cancer by downregulating NBL1 and activating the BMP2/Smad/ID1 pathway.

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机构： [1]Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, 510180 Guangzhou, Guangdong, China [2]Department of Medical Oncology, Guangzhou First People’s Hospital, Guangzhou Medical University, 510180 Guangzhou, Guangdong, China [3]Division of Hematology andOncology, Comprehensive Cancer Center, the University of Alabama at Birmingham, Birmingham, AL 35233, USA [4]International Institute for Translational Chinese Medicine,Guangzhou University of Chinese Medicine, 510006 Guangzhou, Guangdong, China

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Little is known about the biological functions of neuron-specific enolase (NSE) as a specific biomarker for small-cell lung cancer (SCLC). Herein, we elucidate the effect and mechanism of NSE on SCLC stem cell-like characteristics. Upregulated NSE expression was observed in spheroid cells. The gain-of-function and loss-of-function approaches demonstrated that modulation of NSE positively regulated cell proliferation, drug resistance, spherical clone formation, tumor growth, and stem cell-like characteristics of SCLC cells. Mechanistic studies revealed that NSE might downregulate the expression of neuroblastoma suppressor of tumorigenicity 1 (NBL1) by interacting with NBL1, thereby attenuating the competitive inhibitory effect of NBL1 on BMP2 and enhancing the interaction between BMP2 and BMPR1A; this, in turn, may activate the BMP2/Smad/ID1 pathway and promote SCLC stem cell-like characteristics. Moreover, overexpression of NBL1or knockdown of BMP2 rescued the NSE-induced stem cell-like characteristics. In clinical specimens, NSE expression was positively associated with ALDH1A1 expression and negatively correlated with NBL1 expression. High NSE and ALDH1A1 expressions and low NBL1 expression were correlated with poor prognosis in patients with SCLC. In summary, our study demonstrated that NSE promoted stem cell-like characteristics of SCLC via NBL1 and the activation of the BMP2/Smad/ID1 pathway.© 2022. The Author(s).

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出版当年[2021]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区肿瘤学

第一作者：

第一作者机构： [1]Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, 510180 Guangzhou, Guangdong, China [2]Department of Medical Oncology, Guangzhou First People’s Hospital, Guangzhou Medical University, 510180 Guangzhou, Guangdong, China

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通讯机构： [1]Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, 510180 Guangzhou, Guangdong, China [2]Department of Medical Oncology, Guangzhou First People’s Hospital, Guangzhou Medical University, 510180 Guangzhou, Guangdong, China

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