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作者

Aidi Huang, Junyao Cheng, Yuan Zhan, Feifei Zhou, Yanlu Xuan, Yiting Wang, Qingjie Chen, Hailong Wang, Xinping Xu, Shiwen Luo, Minzhang Cheng

作者单位

Affiliations ¹ Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. ² Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Center for Experimental Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. ³ Institute of Molecular Pathology, Department of Pathology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. ⁴ Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China. ⁵ Department of Oncology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. ⁶ Department of Nuclear Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. ⁷ Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Center for Experimental Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. shiwenluo@ncu.edu.cn. ⁸ Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. mzcheng@ncu.edu.cn. ⁹ Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Center for Experimental Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China. mzcheng@ncu.edu.cn.

刊名

Cellular oncology (Dordrecht, Netherlands)

年份

2024

卷号

Vol.47 No.4

页码

1405-1423

ISSN

2211-3436

关键词

EGFR Hedgehog signaling, Ptch1 Non-small cell lung cancer (NSCLC).

摘要

Purpose: The hyperactivation of epidermal growth factor receptor plays a crucial role in non-small cell lung cancer . Hedgehog signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth. Methods: Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistoch...更多

Purpose: The hyperactivation of epidermal growth factor receptor plays a crucial role in non-small cell lung cancer . Hedgehog signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth. Methods: Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting. Results: Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth. Conclusion: Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.收起

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