Secretagogin Downregulation Impairs Nerve Cell Migration in Hirschsprung Disease via Inhibition of the LEF-1/NCAM1 Axis

Yun Zhou; Shuiqing Chi; Shuai Li; Zhibin Luo; Liying Rong; Mengxin Zhang; Yunshang Chen; Jialing Guo; Dehua Yang; Xi Zhang; Guoqing Cao; Shao-Tao Tang

doi:10.1016/j.mcpro.2025.101032

Secretagogin Downregulation Impairs Nerve Cell Migration in Hirschsprung Disease via Inhibition of the LEF-1/NCAM1 Axis

Mol Cell Proteomics. 2025 Jul 11:101032. doi: 10.1016/j.mcpro.2025.101032. Online ahead of print.

Authors

Yun Zhou¹, Shuiqing Chi², Shuai Li², Zhibin Luo², Liying Rong², Mengxin Zhang², Yunshang Chen³, Jialing Guo⁴, Dehua Yang², Xi Zhang², Guoqing Cao², Shao-Tao Tang⁵

Affiliations

¹ Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China.
² Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³ Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China.
⁴ Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of medicine, Hangzhou, 310000, China.
⁵ Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: tshaotao83@hust.edu.cn.

PMID: 40653016
DOI: 10.1016/j.mcpro.2025.101032

Abstract

Hirschsprung disease (HSCR) is a common peripheral neurodevelopmental disorder, and impaired enteric neural crest cell (ENCC) migration is one of the key factors. Secretagogin (SCGN) has been demonstrated to play a critical role in the rostral migratory stream during central nerve regeneration. However, there is a paucity of knowledge on the role of SCGN in ENCC migration. Here we revealed a significant downregulation of SCGN by protein profiles using tandem mass tag (TMT) in HSCR lesion colon tissues. We identified decreased expression of SCGN could hinder cell migration in vitro and in vivo. Mechanistically, SCGN upregulated the transcription factor LEF-1, which directly activated the transcription of the cell adhesion molecule NCAM1, thereby promoting cell migration. In conclusion, this study elucidates the role of SCGN in HSCR pathogenesis by demonstrating its involvement in affecting neural crest cell migration through the LEF-1/NCAM1 axis. The findings could contribute to the diagnostic and therapeutic strategies for HSCR.

Keywords: ENS migration; Hirschsprung disease; NCAM1; SCGN.