The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype.
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http://dx.doi.org/10.3892/or.2017.5656 | DOI Listing |
bioRxiv
November 2024
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Single-cell omics is advancing our understanding of selective neuronal vulnerability in Alzheimer's disease (AD), revealing specific subtypes that are either susceptible or resilient to neurodegeneration. Using single-nucleus and spatial transcriptomics to compare neocortical regions affected early (prefrontal cortex and precuneus) or late (primary visual cortex) in AD, we identified a resilient excitatory population in layer 4 of the primary visual cortex expressing , , and . Layer 4 neurons in association neocortex also remained relatively preserved as AD progressed and shared overlapping molecular signatures of resilience.
View Article and Find Full Text PDFHum Brain Mapp
December 2024
Georgia Institute of Technology, Atlanta, Georgia, USA.
Multimodal learning has emerged as a powerful technique that leverages diverse data sources to enhance learning and decision-making processes. Adapting this approach to analyzing data collected from different biological domains is intuitive, especially for studying neuropsychiatric disorders. A complex neuropsychiatric disorder like schizophrenia (SZ) can affect multiple aspects of the brain and biologies.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, 1089 Budapest, Hungary.
Mounting evidence supports the key role of the disrupted integrity of the blood-brain barrier (BBB) in stress- and inflammation-associated depression. We assumed that variations in genes regulating the expression and coding proteins constructing and maintaining this barrier, along with those involved in inflammation, have a predisposing or protecting role in the development of depressive symptoms after experiencing severe stress. To prove this, genome-by-environment (GxE) interaction analyses were conducted on 6.
View Article and Find Full Text PDFFront Immunol
September 2024
Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
Introduction: AXL receptor expression is proposed to confer immune-checkpoint inhibitor (ICI)-resistance in non-small cell lung cancer (NSCLC) patients. We sought to interrogate AXL expression in conjunction with mutational and tumor-microenvironmental features to uncover predictive mechanisms of resistance in ICI-treated NSCLC patients.
Methods: Tumor samples from 111 NSCLC patients treated with ICI-monotherapy were analyzed by immunohistochemistry for tumor- and immune-AXL expression.
Biol Sex Differ
August 2024
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 160, Los Angeles, CA, 90048, USA.
Background: Fetal sex and placental development impact pregnancy outcomes and fetal-maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies.
Methods: Pregnant subjects were recruited in late first trimester (weeks 10-14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births.
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