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Therapeutic Potential of Targeting the SUMO Pathway in Cancer
<p> The small ubiquitin-like modifier (SUMO) pathway regulates the hallmark properties of cancer cells. Moreover, alterations in activity and in levels of SUMO machinery components have been observed in human cancer. Due ...
Good guy in bad company: How STRNs convert PP2A into an oncoprotein
<p>Certain Protein Phosphatase 2A (PP2A) complexes are human tumor suppressors. In contrast, a paper in this issue of Cancer Cell and two other recent studies demonstrate that PP2A-STRN3/4 complexes inactivate Hippo tumor suppressor pathway, resulting in YAP activation and tumorigenesis. Furthermore, this new oncogenic phosphatase mechanism may be druggable<br></p>...
AutoCoEv-A High-Throughput In Silico Pipeline for Predicting Inter-Protein Coevolution
Protein-protein interactions govern cellular processes via complex regulatory networks, which are still far from being understood. Thus, identifying and understanding connections between proteins can significantly facilitate ...
An unbiased in vitro screen for activating epidermal growth factor receptor mutations
Cancer tissues harbor thousands of mutations, and a given oncogene may
be mutated at hundreds of sites. Yet, only a few of these mutations have
been functionally tested. Here, we describe an unbiased platform for
the ...
Dynamic covalent macrocycles co-delivering genes and drugs against drug-resistant cancer
<p>Polymeric carriers have dominated the development of delivering chemotherapeutic drugs and genes against drug-resistant cancer. However, the biocompatibility, loading, and release capabilities of polymers are unsatisfactory. Here, we have advanced the delivery system by developing dynamic covalent macrocycles using a dithiol monomer through a thiol/disulfide exchange reaction to co-deliver doxorubicin (DOX) and small interfering RNA (siRNA). Our thermodynamically based macrocycles achieve a drug-loading content of 30.2%, whereas a disulfide polymer prepared from the same monomer under kinetic control cannot load DOX. In combination with siRNA, the macrocycles exhibit excellent delivery efficiency and enhanced anti-tumor efficacy in vitro without systemic toxicity. Our findings suggest that dynamic covalent chemistry offers a powerful strategy for exploring macrocyclic carriers that could replace conventional polymers for co-delivery systems, paving the way to more efficient clinic therapies.<br></p>...
An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations
<p>Despite the relatively high frequency of somatic <i>ERBB4</i> mutations in various cancer types, only a few activating <i>ERBB4</i> mutations have been characterized, primarily due to lack of mutational hotspots in ...
Head and neck squamous cell carcinoma cell lines have an immunomodulatory effect on macrophages independent of hypoxia and toll-like receptor 9
<p><b>Background:</b> A low tissue oxygen level, < 1% O-2, is a typical characteristic inside of solid tumors in head and neck cancer (HNSCC) affecting a wide array of cell populations, such as macrophages. However, the ...
An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation
The ErbB4 receptor isoforms JM-a and JM-b differ within their extracellular juxtamembrane (eJM) domains. Here, ErbB4 isoforms are used as a model to address the effect of structural variation in the eJM domain of receptor ...
Small-Molecule-based Supramolecular Plastics Mediated by Liquid-Liquid Phase Separation
<p>Plastics are one of the most widely used polymeric materials. However, they are often undegradable and non-recyclable due to the very stable covalent bonds of macromolecules, causing environmental pollution and health ...