ArticleCancer biology & therapy2014
Downregulation of GRHL2 inhibits the proliferation of colorectal cancer cells by targeting ZEB1.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
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- GRHL2 Regulation of Growth/Motility Balance in Luminal versus Basal Breast Cancer.International journal of molecular sciences · 2023Article
- GRHL2-controlled gene expression networks in luminal breast cancer.Cell communication and signaling : CCS · 2023Article
- GRHL2 Enhances Phosphorylated Estrogen Receptor (ER) Chromatin Binding and Regulates ER-Mediated Transcriptional Activation and Repression.Molecular and cellular biology · 2022Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- Abnormal GRHL2 Methylation Confers Malignant Progression to Acute Leukemia.Applied bionics and biomechanics · 2022Article
- Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT.Oncotarget · 2020Article
- Immune-related genes in tumor-specific CD4BMC cancer · 2020Article
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- Grainyhead-like transcription factors in cancer - Focus on recent developments.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Spotlight on the Granules (Grainyhead-Like Proteins) - From an Evolutionary Conserved Controller of Epithelial Trait to Pioneering the Chromatin Landscape.Frontiers in molecular biosciences · 2020Review
- Grainyhead-like 2 as a double-edged sword in development and cancer.American journal of translational research · 2020Review
- GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process.OncoTargets and therapy · 2020Article
- Grainyhead-Like Genes Family May Act as Novel Biomarkers in Colon Cancer.OncoTargets and therapy · 2020Article
- The integrative knowledge base for miRNA-mRNA expression in colorectal cancer.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous reports have associated GRHL2 with tumor progression. However, the biological role of GRHL2 in human colorectal cancer (CRC) has not been explored. We examined the expression of GRHL2 in 75 CRC samples, as well as the paired non-tumor tissues, by immunohistochemistry, qRT-PCR, and western blot analysis. The association between GRHL2 expression and various clinicopathological parameters including Ki-67, a marker of proliferative activity, was also evaluated. We performed lentivirus-mediated shRNA transfection to knock down GRHL2 gene expression in HT29 and HCT116 CRC cells. Cell proliferation was examined by the CCK-8 (Cell Counting Kit-8) assay, colony formation, and cell cycle assay in vitro. Tumorigenesis in vivo was assessed using a mouse xenograft model. Moreover, we transiently silenced ZEB1 expression in GRHL2-knockdown CRC cells using specific shRNA, and then examined the effects on GRHL2 and E-cadherin expression, as well as cell proliferation. Herein, we demonstrated that enhanced GRHL2 expression was detected in CRC, and correlated with higher levels of Ki-67 staining, larger tumor size, and advanced clinical stage. Knocking down GRHL2 in HT29 and HCT116 CRC cells significantly inhibited cell proliferation by decreasing the number of cells in S phase and increasing that in the G 0/G 1 phaseof the cell cycle. This resulted in inhibition of tumorigenesis in vivo, as well as increased expression of ZEB1. Furthermore, transient ZEB1 knockdown dramatically enhanced cell proliferation and increased GRHL2 and E-cadherin expression. Collectively, our study has identified ZEB1 as a target of GRHL2 and suggested a reciprocal GRHL2-ZEB1 repressive relationship, providing a novel mechanism through which proliferation may be modulated in CRC cells.
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