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Updated: Feb 2, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Knockdown GREM1 suppresses cell growth, angiogenesis, and epithelial-mesenchymal transition in colon cancer
Yan Liu1, Yongchao Li2, Ruizhe Hou3,3
1Department of Ultrasonography, China-Japan Union Hospital, Jilin University, Changchun, China.
Abstract:
Gremlin 1 (GREM1), as a bone morphogenetic protein (BMP) antagonist and vascular endothelial growth factor receptor-2 (VEGFR2) novel agonist, has been confirmed as overexpressed in colorectal cancer (CRC) tissues but its role in carcinogenesis remains unclear. Here we reported that the GREM1 expression in mesenchymal-like colon cancer cells (SW620 and SW480) was significantly higher than that of epithelial-like colon cancer cells (Caco-2, HTC116, and HT29) and normal colon cell. Simultaneously, we analyzed two series of CRC transcriptomes from Gene Expression Omnibus (GEO) databases and found the great majority of primary CRC tissues expressed high level of GREM1 messenger RNA (mRNA) compared with adjacent normal tissues, and that the GREM1 mRNA expression is correlated with low histological grade development and stage 2 to 3 metastatic recurrence in CRC based on a data analysis of 104 different stage CRC tissue from the GEO databases. Functional studies showed that GREM1 silencing by short hairpin RNA (shRNA) significantly inhibited CRC cells proliferation, migration, the formation of vascular endothelial growth factor (VEGF)-induced capillary structure of human umbilical vein endothelial cells (HUVECs), and epithelial-mesenchymal transition in colon cancer cells by repressing phosphorylation levels of BMP downstream signal Smad1, vascular endothelial growth factor (VEGF) downstream signal matrix metallopeptidase 2 (MMP2), and metastasis-related factor C-X-C motif chemokine ligand 12 (CXCL12) expression. In addition, shGREM1 combined with VEGF inhibitor BAW2881 displayed more effective antiangiogenesis to inhibit the tube formation of HUVEC. Hence, these experiments demonstrated that GREM1 is involved in CRC development and procession and provide a new idea for CRC diagnosis, resistance therapy, and prognosis.
Insights
Gremlin 1 (GREM1) is overexpressed in colorectal cancer (CRC) and drives tumor growth and metastasis. Inhibiting GREM1 shows promise for CRC therapy and improving patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gremlin 1 (GREM1) is a known bone morphogenetic protein (BMP) antagonist and vascular endothelial growth factor receptor-2 (VEGFR2) agonist.
- GREM1 is overexpressed in colorectal cancer (CRC) tissues, but its specific role in carcinogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of GREM1 in colorectal cancer (CRC) development, progression, and potential as a therapeutic target.
Main Methods:
- Comparative analysis of GREM1 expression in different colon cancer cell lines and CRC tissues using Gene Expression Omnibus (GEO) databases.
- Functional studies involving GREM1 silencing via short hairpin RNA (shRNA) in CRC cells.
- Assessment of GREM1's impact on cell proliferation, migration, epithelial-mesenchymal transition (EMT), and angiogenesis.
- Combination therapy evaluation with a vascular endothelial growth factor (VEGF) inhibitor.
Main Results:
- GREM1 expression was significantly higher in mesenchymal-like CRC cells and primary CRC tissues compared to normal cells and tissues.
- GREM1 overexpression correlated with lower histological grade and stage 2-3 metastatic recurrence in CRC.
- GREM1 silencing inhibited CRC cell proliferation, migration, EMT, and VEGF-induced angiogenesis.
- GREM1 silencing repressed key signaling pathways including BMP, VEGF, and CXCL12.
- Combined GREM1 inhibition and VEGF inhibition demonstrated enhanced anti-angiogenic effects.
Conclusions:
- GREM1 plays a significant role in colorectal cancer (CRC) development and progression.
- GREM1 is a potential biomarker for CRC diagnosis and prognosis.
- Targeting GREM1, potentially in combination with anti-VEGF therapies, offers a novel strategy for CRC treatment.
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