.png){kind=icon}
.png){kind=icon}
Return
Integrative transcriptomic and experimental analysis identifies GREM1 as a pro-metastatic mediator in lung adenocarcinoma
.png){kind=icon}
OA
AI
Z
H
K
B
DOI：10.1186/s12967-026-08793-9.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
The TGF-β signaling pathway can effectively activate epithelial-mesenchymal transition and glycolysis, thereby promoting tumor metastasis and drug resistance. Bioinformatics analyses have indicated that GREM1 may facilitate tumor progression and metastasis. However, the mechanism by which GREM1 promotes metastasis in lung adenocarcinoma remains largely unknown. We applied pathway-focused integrative clustering to characterize molecular subgroups demonstrating differential activation of EMT, glycolysis and TGF-β pathways, subsequently developing different prognosis subtypes. Comprehensive functional investigations encompassing wound healing assays, migration, invasion, apoptosis evaluations and metastasis models were performed to elucidate GREM1’s role in cancer progression. Mechanistic explorations through WB, co-IP techniques and virtual knockout revealed critical downstream effectors and signaling networks modulated by GREM1 activity. Integrative clustering identified two LUAD subtypes with distinct oncogenic pathways activity and different survival outcomes. GREM1 was prioritized as a CS2-associated core gene and was associated with poor prognosis. Functional assays showed that GREM1 enhanced LUAD cell migration, invasion, glucose uptake, and lung metastatic colonization, while suppressing apoptosis. Mechanistically, GREM1 interacts with BMP2 and induces epithelial–mesenchymal transition and glycolysis via the TGF-β signaling pathway, thereby promoting LUAD progression and metastasis. GREM1 emerges as both a metastasis driver and therapeutic target, offering opportunities for biomarker-guided precision oncology.
Keywords:
Lung adenocarcinoma
GREM1
EMT
TCGA
GEO
Journal
IF:
7.5
Papers:
9.3K
Citations:
3.2W
Organization
Cited Papers