ArticlePloS one2015
Inhibitory mechanism of FAT4 gene expression in response to actin dynamics during Src-induced carcinogenesis.
Article in PloS one, 2015. 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, 22 citations in OpenAlex.
- Research on the role and mechanism of FAT4 in the development and progression of tumor and non-tumor diseases.Discover oncology · 2026Review
- Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.British journal of cancer · 2024Article
- Muscle Transcriptome Sequencing Revealed Thermal Stress-Responsive Regulatory Genes in Farmed Rohu, Labeo rohita (Hamilton, 1822).Marine biotechnology (New York, N.Y.) · 2023Article
- Matrix stiffness induces Drp1-mediated mitochondrial fission through Piezo1 mechanotransduction in human intervertebral disc degeneration.Journal of translational medicine · 2023Article
- Dysregulation of the Scribble/YAP/β-catenin axis sustains the fibroinflammatory response in a PKHD1FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Biomarker LEPRE1 induces pelitinib-specific drug responsiveness by regulating ABCG2 expression and tumor transition states in human leukemia and lung cancer.Scientific reports · 2022Article
- Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion.Molecular biology of the cell · 2020Article
- Review
- FAT4 silencing promotes epithelial-to-mesenchymal transition and invasion via regulation of YAP and β-catenin activity in ovarian cancer.BMC cancer · 2020Article
- Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway.Cancer gene therapy · 2019Article
- FAT4-USP51 complex regulates the proliferation and invasion of endometrial cancer via Hippo pathway.American journal of translational research · 2019Article
- Application of unique sequence index (USI) barcode to gene expression profiling in gastric adenocarcinoma.Journal of cell communication and signaling · 2017Article
- FAT4 hypermethylation and grade dependent downregulation in gastric adenocarcinoma.Journal of cell communication and signaling · 2017Article
- Proteomic Dissection of Nanotopography-Sensitive Mechanotransductive Signaling Hubs that Foster Neuronal Differentiation in PC12 Cells.Frontiers in cellular neuroscience · 2017Article
- Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells.International journal of molecular sciences · 2016Review
- LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.BMC biology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic transformation is characterized by morphological changes resulting from alterations in actin dynamics and adhesive activities. Emerging evidence suggests that the protocadherin FAT4 acts as a tumor suppressor in humans, and reduced FAT4 gene expression has been reported in breast and lung cancers and melanoma. However, the mechanism controlling FAT4 gene expression is poorly understood. In this study, we show that transient activation of the Src oncoprotein represses FAT4 mRNA expression through actin depolymerization in the immortalized normal human mammary epithelial cell line MCF-10A. Src activation causes actin depolymerization via the MEK/Erk/Cofilin cascade. The MEK inhibitor U0126 blocks the inhibitory effect of Src on FAT4 mRNA expression and Src-induced actin depolymerization. To determine whether actin dynamics act on the regulation of FAT4 mRNA expression, we treated MCF-10A cells with the ROCK inhibitor Y-27632. Y-27632 treatment decreased FAT4 mRNA expression. This suppressive effect was blocked by siRNA-mediated knockdown of Cofilin1. Furthermore, simultaneous administration of Latrunculin A (an actin depolymerizing agent), Y-27632, and Cofilin1 siRNA to the cells resulted in a marked reduction of FAT4 mRNA expression. Intriguingly, we also found that FAT4 mRNA expression was reduced under both low cell density and low stiffness conditions, which suggests that mechanotransduction affects FAT4 mRNA expression. Additionally, we show that siRNA-mediated FAT4 knockdown induced the activity of the Hippo effector YAP/TAZ in MCF-10A cells. Taken together, our results reveal a novel inhibitory mechanism of FAT4 gene expression through actin depolymerization during Src-induced carcinogenesis in human breast cells.
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