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Keywords = cell-targeting peptide
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8 pages, 1823 KB  
Brief Report
The CK2/ECE1c Partnership: An Unveiled Pathway to Aggressiveness in Cancer
by Karla Villalobos-Nova, María de los Ángeles Toro, Pablo Pérez-Moreno, Ignacio Niechi and Julio C. Tapia
Kinases Phosphatases 2024, 2(1), 1-8; https://doi.org/10.3390/kinasesphosphatases2010001 - 19 Dec 2023
Cited by 2 | Viewed by 2034
Abstract
The endothelin-1 (ET1) peptide has a pathological role in the activation of proliferation, survival and invasiveness pathways in different cancers. ET1’s effects rely on its activation by the endothelin-converting enzyme-1 (ECE1), which is expressed as four isoforms, differing only in their cytoplasmic N-terminuses. [...] Read more.
The endothelin-1 (ET1) peptide has a pathological role in the activation of proliferation, survival and invasiveness pathways in different cancers. ET1’s effects rely on its activation by the endothelin-converting enzyme-1 (ECE1), which is expressed as four isoforms, differing only in their cytoplasmic N-terminuses. We already demonstrated in colorectal cancer, glioblastoma, and preliminarily lung cancer, that the isoform ECE1c heightens aggressiveness by promoting cancer stem cell traits. This is achieved through a non-canonical ET1-independent mechanism of enhancement of ECE1c’s stability upon CK2-dependent phosphorylation at S18 and S20. Here, a K6 residue is presumably responsible for ECE1c ubiquitination as its mutation to R impairs proteasomal degradation. However, how phosphorylation enhances ECE1c’s stability and how this translates into aggressiveness are still open questions. In this brief report, by swapping residues to either phospho-mimetic or phospho-resistant amino acids, we propose that the N-terminus may also be phosphorylated at Y5 and/or T9 by an unknown kinase(s). In addition, N-terminus phosphorylation may lead to a blockage of K6 ubiquitination, increasing ECE1c’s stability and presumably activating the Wnt/β-catenin signaling pathway. Thus, a novel CK2/ECE1c partnership may be emerging to promote aggressiveness and thus become a biomarker of poor prognosis and a potential therapeutic target for several cancers. Full article
(This article belongs to the Special Issue Past, Present and Future of Protein Kinase CK2 Research)
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14 pages, 527 KB  
Article
Mesoporous Silica Nanoparticles with Co-Condensed Gadolinium Chelates for Multimodal Imaging
by Kathryn M. L. Taylor-Pashow, Joseph Della Rocca and Wenbin Lin
Nanomaterials 2012, 2(1), 1-14; https://doi.org/10.3390/nano2010001 - 27 Dec 2011
Cited by 27 | Viewed by 9499
Abstract
Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd3+ complexes at very high loadings (15.5–28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety [...] Read more.
Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd3+ complexes at very high loadings (15.5–28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety of methods including SEM and TEM, nitrogen adsorption measurements, thermogravimetric analysis (TGA), direct current plasma (DCP) spectroscopy, and powder X-ray diffraction (PXRD). The magnetic resonance (MR) relaxivities of these contrast agents were determined using a 3 T MR scanner. The r1 relaxivities of these nanoparticles range from 4.1 to 8.4 mM−1s−1 on a per Gd basis. Additionally, the MSN particles were functionalized with an organic fluorophore and cancer cell targeting peptide to allow for demonstration of both the optical and MR contrast enhancing capabilities in vitro. Full article
(This article belongs to the Special Issue From Molecules to Nanomaterials)
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