ROCK signaling causes epidermal hyper-proliferation by increasing ECM production, elevating dermal stiffness, and enhancing Fak-mediated mechano-transduction signaling. Elevated dermal stiffness in turn causes ROCK activation, establishing mechano-reciprocity, a positive feedback loop that can promote tumors. We have identified a negative feedback mechanism that limits excessive ROCK signaling during wound healing and is lost in squamous cell carcinomas (SCCs). Signal flux through ROCK was selectively tuned down by increased levels of 14-3-3ζ, which interacted with Mypt1, a ROCK signaling antagonist. In 14-3-3ζ(-/-) mice, unrestrained ROCK signaling at wound margins elevated ECM production and reduced ECM remodeling, increasing dermal stiffness and causing rapid wound healing. Conversely, 14-3-3ζ deficiency enhanced cutaneous SCC size. Significantly, inhibiting 14-3-3ζ with a novel pharmacological agent accelerated wound healing 2-fold. Patient samples of chronic non-healing wounds overexpressed 14-3-3ζ, while cutaneous SCCs had reduced 14-3-3ζ. These results reveal a novel 14-3-3ζ-dependent mechanism that negatively regulates mechano-reciprocity, suggesting new therapeutic opportunities.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.devcel.2015.11.026 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.
Nat Cancer
January 2025
Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).
View Article and Find Full Text PDFAnalysis and Categorization of Various Types of Vocal Distortion in Rock, Metal, Pop Styles, and Throat Singing Observed by High-Speed Digital Imaging.
J Voice
January 2025
Faculty of Design, Kyushu University, 4-9-1 Shiobaru, Minami-ku, Fukuoka 815-8540, Japan.
Introduction: Vocal distortion, also known as a scream or growl, is used worldwide as an essential technique in singing, especially in rock and metal, and as an ethnic voice in Mongolian singing. However, the production mechanism of vocal distortion is not yet clearly understood owing to limited research on the behavior of the larynx, which is the source of the distorted voice.
Objectives: This study used high-speed digital imaging (HSDI) to observe the larynx of professional singers with exceptional singing skills and determine the laryngeal dynamics in the voice production of various vocal distortions.
This study characterizes a fluorescent -tdTomato neuronal reporter mouse line with strong labeling of axons throughout the optic nerve, of retinal ganglion cell (RGC) soma in the ganglion cell layer (GCL), and of RGC dendrites in the inner plexiform layer (IPL). The model facilitated assessment of RGC loss in models of degeneration and of RGC detection in mixed neural/glial cultures. The tdTomato signal showed strong overlap with >98% cells immunolabeled with RGC markers RBPMS or BRN3A, consistent with the ubiquitous presence of the vesicular glutamate transporter 2 (VGUT2, SLC17A6) in all RGC subtypes.
View Article and Find Full Text PDFHistochemical indications for a chemically complex signal produced by the cervical gill slit gland of the pygmy sperm whale (Kogia breviceps).
Anat Rec (Hoboken)
January 2025
Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina, USA.
The pygmy sperm whale (Kogia breviceps) possesses an exocrine gland associated with its false gill slit pigmentation pattern. The cervical gill slit gland is a compound tubuloalveolar gland that produces a holocrine secretion and displays maturational changes in size and secretory histology. While the morphology of the cervical gill slit gland has been described in detail, to date, the chemical composition of its secretion remains uncharacterized.
View Article and Find Full Text PDFCorrigendum to "ROCK inhibition reduces the sensitivity of mutant p53 glioblastoma to genotoxic stress through a Rac1- driven ROS production" [Int. J. Biochem. Mol. Bio. 164 (2023) 106474-106484].
Int J Biochem Cell Biol
January 2025
Laboratory of Signaling in Biomolecular Systems, Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil. Electronic address:
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!