Regulation of neuronal invasion of small cell lung cancer by STMN2/β-alanine-controlled metabolic reprogramming

Cell Reports 2026 Open access

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Authors: Yan Zhou, Runbo Zhong, Yanwei Zhang, Michael R. Shurin, Galina V. Shurin, L. Xiong, Tianqing Chu, Baohui Han, Haohua Teng, Yu Yang, Erpeng Wu, Chao Zhang
+6 more Lincheng Zhang, Wanting Liu, Yuqing Lou, Jun Lu, Yongjie Wang, H. Zhong
DOI: 10.1016/j.celrep.2026.117208
Cited by: 1
References: 41

Abstract

Small cell lung cancer (SCLC) exhibits a high incidence of perineural invasion (PNI), a clinical feature associated with poor prognosis. Here, we establish PNI as an independent adverse prognostic factor in a surgical SCLC cohort. We further show that the neural microenvironment upregulates stathmin-2 (STMN2) in SCLC cells. STMN2, in a concentration-dependent manner, activates the β-alanine metabolic pathway, leading to intracellular β-alanine accumulation, which enhances tumor cell migration and invasion. In vivo, STMN2 knockdown suppresses neural invasion, an effect reversible upon β-alanine supplementation. This work defines a neural-STMN2-β-alanine-invasion axis that drives PNI in SCLC, providing mechanistic insights and highlighting a promising metabolic vulnerability for therapeutic intervention.

Fields of Study & Subjects

Lung Cancer Research Studies Cancer Hypoxia and Metabolism Stress Anesthesia and Immune Response

Publication details

Journal / source
Cell Reports
Publisher
Elsevier BV
Volume
45
Issue
4
Pages
117208–117208
Publication date
28 March 2026
Language
EN