ArticleJournal of experimental & clinical cancer research : CR2016
Gab2 facilitates epithelial-to-mesenchymal transition via the MEK/ERK/MMP signaling in colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer.World journal of gastroenterology · 2016Pooled it
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- Patient-derived mini-colons enable long-term modeling of tumor-microenvironment complexity.Nature biotechnology · 2025Article
- IQGAP1: cross-disease target via receptor-pathway networks.Frontiers in oncology · 2025Review
- Structure optimization and molecular dynamics studies of new tumor-selectiveJournal of enzyme inhibition and medicinal chemistry · 2024Article
- DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma.Translational oncology · 2024Article
- Gab2 promotes the growth of colorectal cancer by regulating the M2 polarization of tumor‑associated macrophages.International journal of molecular medicine · 2024Article
- Silencing ofOncology letters · 2023Article
- Relationship between Epithelial-to-Mesenchymal Transition and Tumor-Associated Macrophages in Colorectal Liver Metastases.International journal of molecular sciences · 2022Review
- Nonylphenol Promoted Epithelial-Mesenchymal Transition in Colorectal Cancer Cells by Upregulating the Expression of Regulator of Cell Cycle.Chemical research in toxicology · 2022Article
- The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms.International journal of molecular sciences · 2022Review
- KIF22 Promotes Development of Pancreatic Cancer by Regulating the MEK/ERK/P21 Signaling Axis.BioMed research international · 2022Article
- The Role of Matrix Metalloproteinases in Endometriosis: A Potential Target.Biomolecules · 2021Review
- Implication of human endogenous retrovirus W family envelope in hepatocellular carcinoma promotes MEK/ERK-mediated metastatic invasiveness and doxorubicin resistance.Cell death discovery · 2021Article
- Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells.BMC cancer · 2021Article
- Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway.Cancer science · 2020Article
- Article
- RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer.International journal of molecular sciences · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGrb2-associated binder 2 (Gab2), a scaffolding adaptor protein, has recently been implicated in cancer progression. However, the role of Gab2 in the progression and metastasis of colorectal cancer (CRC) remains unclear.
methodsGab2 expression was assessed in CRC patient specimens as well as in CRC cell lines. Recombinant lentivirus vector containing Gab2 gene and its small interfering RNAs were constructed and introduced into CRC cells. Cell migration and invasion ability were evaluated by transwell assays in vitro, and in vivo metastasis was performed on nude mice model. Moreover, the expression of Gab2 and epithelial-to-mesenchymal transition (EMT)-associated proteins (E-cadherin and vimentin) were assessed by western blot and qRT-PCR in CRC cells to evaluate the correlation between Gab2 and EMT. Finally, we evaluated the impact of Gab2 on the activation of its downstream signaling effectors, and furthermore the effects of these pathways on Gab2 induced-EMT were also detected.
resultsWe confirmed that increased Gab2 expression correlated with higher tumor node metastasis stage and highly invasive CRC cell lines. Ectopic expression of Gab2 promoted metastasis of CRC cells, whereas silencing of Gab2 resulted in inhibited metastasis both in vitro and in vivo. Overexpression of Gab2 in CRC cells induced EMT, whereas knockdown of Gab2 had the opposite effect. Furthermore, upregulation of Gab2 expression obviously stimulated the activation of extracellular signal-regulated kinase-1/2 (ERK1/2), and increased the expression of matrix metalloproteinase-7 (MMP7) and matrix metalloproteinase-9 (MMP9) in CRC cells. Conversely, downregulation of Gab2 expression significantly decreased the activation of ERK1/2, and inhibited MMP7 and MMP9 expression. U0126, an inhibitor of mitogen-activated protein kinase (MEK), can reverse the effects of Gab2 on EMT.
conclusionsOur work highlights that Gab2 induces EMT through the MEK/ERK/MMP pathway, which in turn promotes intestinal tumor metastasis.
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