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The BCL-2 family proteins are central regulators of apoptosis. However, cells deficient for BAX and BAK or overexpressing BCL-2 still succumb to oxidative stress upon DNA damage or matrix detachment. Here, we show that ΔNp63α overexpression protects cells from oxidative stress induced by oxidants, DNA damage, anoikis, or ferroptosis-inducing agents. Conversely, ΔNp63α deficiency increases oxidative stress. Mechanistically, ΔNp63α orchestrates redox homeostasis through transcriptional control of glutathione biogenesis, utilization, and regeneration. Analysis of a lung squamous cell carcinoma dataset from The Cancer Genome Atlas (TCGA) reveals that TP63 amplification/overexpression upregulates the glutathione metabolism pathway in primary human tumors. Strikingly, overexpression of ΔNp63α promotes clonogenic survival of p53-/-Bax-/-Bak-/- cells against DNA damage. Furthermore, co-expression of BCL-2 and ΔNp63α confers clonogenic survival against matrix detachment, disrupts the luminal clearance of mammary acini, and promotes cancer metastasis. Our findings highlight the need for a simultaneous blockade of apoptosis and oxidative stress to promote long-term cellular well-being.
Pubmed ID: 29212036
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Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsDatabase which provides on-line searching of microarray datasets generated from rat spinal cord after contusion injury. Both the primary injury site and a site 5 mm distal to the injury site were assayed. Tissue was obtained from Long Evans rats subject to spinal cord contusion injury using the MASCIS impactor (formerly known as the NYU impactor). RNA expression was assayed at the site of injury and distal to the site of injury using the Affymetrix Rat Neuro U34 chip.
View all literature mentionsIn vivo imaging software which facilitates workflow for in vivo optical, X-ray and microCT image acquisition, analysis and data organization.
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