Novel function of ∆Np63 in cell polarity and metabolism in pubertal mammary gland development.
Summary of "Novel function of ∆Np63 in cell polarity and metabolism in pubertal mammary gland development."
The ∆Np63 isoform of the p53-family transcription factor Trp63 is a key regulator of mammary epithelial stem cells that is involved in breast cancer development. To investigate the role of ∆Np63 at different stages of normal mammary gland development, we generated a ∆Np63 inducible conditional knockout (cKO) mouse model. We demonstrate that deletion of ∆Np63 at puberty results in depletion of mammary stem cell-enriched basal cells, reduces expression of E-cadherin and β-catenin, and leads to a closed ductal lumen. RNA-sequencing analysis reveals reduced expression of oxidative phosphorylation (OXPHOS)-associated proteins and desmosomal polarity proteins. Functional assays show reduced numbers of mitochondria in the mammary epithelial cells of ΔNp63 cKO compared to wildtype, supporting the reduced OXPHOS phenotype. These findings identify a novel role for ∆Np63 in cellular metabolism and mammary epithelial cell polarity.
Affiliation
Journal Details
This article was published in the following journal.
Name: FEBS letters
ISSN: 1873-3468
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/31794060
- DOI: http://dx.doi.org/10.1002/1873-3468.13703
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Medical and Biotech [MESH] Definitions
Dishevelled Proteins
A family of proteins that are key components of the WNT SIGNALING PATHWAY, where they function downstream of FRIZZLED RECEPTORS. They contain an N-terminal dishevelled-AXIN PROTEIN (DIX) domain, which mediates oligomerization; a central PDZ DOMAIN which binds to the frizzled receptor; and a C-terminal DEP domain which facilitates binding to the CELL MEMBRANE. Dishevelled proteins have important functions in CELL DIFFERENTIATION and establishing CELL POLARITY.
Mammary Neoplasms, Animal
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
Tamoxifen
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
Cell Polarity
Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.
Angiopoietin-like 4 Protein
A secreted angiopoietin-like protein expressed under hypoxic conditions by ENDOTHELIAL CELLS. It inhibits cell proliferation, cell migration, and tubule formation; the inactive form accumulates in the endothelial EXTRACELLULAR MATRIX, reducing vascular leakage. ANGPTL4 has direct roles in regulating glucose and lipid metabolism, as well as INSULIN SENSITIVITY, and may also function as a regulator of angiogenesis and tumorigenesis.
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