ArticleCell adhesion & migration2018
PHLDA1 (pleckstrin homology-like domain, family A, member 1) knockdown promotes migration and invasion of MCF10A breast epithelial cells.
Article in Cell adhesion & migration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Multi-omics profiling reveals PLEKHA6 as a modulator of β-catenin signaling and therapeutic vulnerability in lung adenocarcinoma.American journal of cancer research · 2025Article
- Expanding on roles of pleckstrin homology-like domain family A member 1 protein.Cell and tissue research · 2025Review
- PHLDA1-PRDM1 mediates the effect of lentiviral vectors on fate-determination of human retinal progenitor cells.Cellular and molecular life sciences : CMLS · 2024Article
- Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.Current issues in molecular biology · 2024Article
- Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma.International journal of molecular sciences · 2022Article
- Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma.Journal of thoracic disease · 2021Article
- A Novel 8-Gene Prognostic Signature for Survival Prediction of Uveal Melanoma.Analytical cellular pathology (Amsterdam) · 2021Article
- Whole-exome sequencing of familial esophageal squamous cell carcinoma identified rare pathogenic variants in new predisposition genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Article
- PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer.Cell reports · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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Abstract
PHLDA1 (pleckstrin homology-like domain, family A, member 1) is a multifunctional protein that plays distinct roles in several biological processes including cell death and therefore its altered expression has been identified in different types of cancer. Progressively loss of PHLDA1 was found in primary and metastatic melanoma while its overexpression was reported in intestinal and pancreatic tumors. Previous work from our group showed that negative expression of PHLDA1 protein was a strong predictor of poor prognosis for breast cancer disease. However, the function of PHLDA1 in mammary epithelial cells and the tumorigenic process of the breast is unclear. To dissect PHLDA1 role in human breast epithelial cells, we generated a clone of MCF10A cells with stable knockdown of PHLDA1 and performed functional studies. To achieve reduced PHLDA1 expression we used shRNA plasmid transfection and then changes in cell morphology and biological behavior were assessed. We found that PHLDA1 downregulation induced marked morphological alterations in MCF10A cells, such as changes in cell-to-cell adhesion pattern and cytoskeleton reorganization. Regarding cell behavior, MCF10A cells with reduced expression of PHLDA1 showed higher proliferative rate and migration ability in comparison with control cells. We also found that MCF10A cells with PHLDA1 knockdown acquired invasive properties, as evaluated by transwell Matrigel invasion assay and showed enhanced colony-forming ability and irregular growth in low attachment condition. Altogether, our results indicate that PHLDA1 downregulation in MCF10A cells leads to morphological changes and a more aggressive behavior.
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