ArticleCancer biology & therapy2013
Targeting the ERK pathway reduces liver metastasis of Smad4-inactivated colorectal cancer.
Article in Cancer biology & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Myeloid EGFR deficiency accelerates recovery from AKI via macrophage efferocytosis and neutrophil apoptosis.Nature communications · 2025Article
- Detecting colorectal cancer using genetic and epigenetic biomarkers: screening and diagnosis.Journal of medicine and life · 2024Review
- The m6A modification-mediated OGDHL exerts a tumor suppressor role in ccRCC by downregulating FASN to inhibit lipid synthesis and ERK signaling.Cell death & disease · 2023Article
- Review
- Concomitant MEK and Cyclin Gene Alterations: Implications for Response to Targeted Therapeutics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.Oncology reports · 2021Article
- Emerging Mechanisms and Treatment Progress on Liver Metastasis of Colorectal Cancer.OncoTargets and therapy · 2021Review
- TGF-β signaling in liver metastasis.Clinical and translational medicine · 2020Review
- Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment.International journal of molecular sciences · 2019Review
- SMAD4 Y353C promotes the progression of PDAC.BMC cancer · 2019Article
- Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis.Journal of experimental & clinical cancer research : CR · 2019Article
- Integrated Genomic, Epigenomic, and Expression Analyses of Ovarian Cancer Cell Lines.Cell reports · 2018Article
- Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1.Theranostics · 2018Article
- Caveolin-1 promotes Ewing sarcoma metastasis regulating MMP-9 expression through MAPK/ERK pathway.Oncotarget · 2016Article
- TAp73 loss favors Smad-independent TGF-β signaling that drives EMT in pancreatic ductal adenocarcinoma.Cell death and differentiation · 2016Article
- CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor β (TGF-β)/Smad signaling is involved in colorectal carcinoma (CRC) development and progression. The frequent loss of SMAD4 is associated with liver metastasis and poor prognosis of CRC, but the underlying mechanism remains elusive. This study aimed to elucidate the role of Smad-independent TGF-β signaling in CRC metastasis. Immunohistochemistry showed that Smad4 level was negatively correlated with TNM stage and phospho-ERK level in human CRCs and liver metastasis samples. Knockdown of Smad4 in CT26 and HCT116 cells activated ERK pathway, altered the expression of MMP2 and COX-2, promoted cell motility, migration, and invasion in vitro, enhanced metastasis, and shortened the survival of metastatic tumor-bearing mice. MEK inhibitor U0126 and GSK1120212 inhibited the motility, migration, and invasion of Smad4 knockdown cells, inhibited metastasis, and prolonged the survival of metastatic tumor-bearing mice. Furthermore, MEK inhibitor could reverse the changes of phospho-ERK, MMP2, and COX-2 levels. In conclusion, our results indicate that ERK pathway plays a key oncogenic role in CRC with SMAD4 inactivation mutations, and implicate ERK as a potential therapeutic target for CRC liver metastasis.
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