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LRRC15 Promotes Proliferation and Metastasis of Lung Squamous Cell Carcinoma by Activating the PI3K/AKT and FAK Signaling Pathways


ZHANG Yuting1, HU Qing1, HUANG Jiafu1, GU Yiwen1, ZHU Rui2, LIU Pan2, SU Dan2, YING Lisha1,2*

(1Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou 310011, China; 2Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou 310011, China)
Abstract:

LRRC15 is a member of the leucine-rich repeat protein family. This study aims to investigate the functional role of LRRC15 in LUSC (lung squamous cell carcinoma) and its underlying molecular mechanisms. By integrating public databases including cBioPortal, TIMER2.0, UALCAN, and CPTAC with transcriptome sequenc ing data from 42 clinical samples in laboratory, identified abnormally high LRRC15 expression in LUSC tissues. Its expression levels were significantly correlated with tumor progression and poor patient prognosis. In functional ex periments, we established stably overexpressing LRRC15 cell lines. CCK-8 proliferation assays, cell scratch assays, and Transwell migration assays confirmed that LRRC15 overexpression significantly enhances the proliferation and migration capabilities of LUSC cells. Further bioinformatics analysis based on TCGA data suggested that LRRC15 may influence tumor cell malignant behavior by regulating the PI3K/AKT signaling pathway and ECM (extracellular matrix) remodeling. Western blot experiments validated that LRRC15 overexpression significantly upregulates the phosphorylation levels of AKT and FAK. In summary, LRRC15 may drive LUSC cell proliferation and migration through dual mechanisms: activating the PI3K/AKT signaling pathway and promoting ECM remodeling. Its over expression serves as a potential biomarker for poor prognosis in LUSC patients and provides new research direc tions for targeted therapy in lung squamous cell carcinoma.


CSTR: 32200.14.cjcb.2026.03.0016