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“[...] we have characterized a pair of compounds that impact multiple processes that are relevant to cancer cell proliferation but also, and possibly more importantly, to metastasis [...].”
BUFFALO, NY- May 20, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 16, 2024, entitled, “The anticancer potential of the CLK kinases inhibitors 1C8 and GPS167 revealed by their impact on the epithelial-mesenchymal transition and the antiviral immune response.”
The diheteroarylamide-based compound 1C8 and the aminothiazole carboxamide-related compound GPS167 inhibit the CLK kinases, and affect the proliferation of a broad range of cancer cell lines. A chemogenomic screen previously performed with GPS167 revealed that the depletion of components associated with mitotic spindle assembly altered sensitivity to GPS167.
In this new study, researchers Lulzim Shkreta, Johanne Toutant, Aurélie Delannoy, David Durantel, Anna Salvetti, Sophie Ehresmann, Martin Sauvageau, Julien A. Delbrouck, Alice Gravel-Trudeau, Christian Comeau, Caroline Huard, Jasmin Coulombe-Huntington, Mike Tyers, David Grierson, Pierre-Luc Boudreault, and Benoit Chabot from Université de Sherbrooke, Université de Lyon, Institut de recherches cliniques de Montréal, Université de Montréal, and University of British Columbia a similar screen performed with 1C8 also established the impact of components involved in mitotic spindle assembly.
“Accordingly, transcriptome analyses of cells treated with 1C8 and GPS167 indicated that the expression and RNA splicing of transcripts encoding mitotic spindle assembly components were affected.”
The functional relevance of the microtubule connection was confirmed by showing that subtoxic concentrations of drugs affecting mitotic spindle assembly increased sensitivity to GPS167. 1C8 and GPS167 impacted the expression and splicing of transcripts in pathways relevant to tumor progression, including MYC targets and the epithelial mesenchymal transition (EMT). Finally, 1C8 and GPS167 altered the expression and alternative splicing of transcripts involved in the antiviral immune response. Consistent with this observation, depleting the double-stranded RNA sensor DHX33 suppressed GPS167-mediated cytotoxicity on HCT116 cells.
“Our study uncovered molecular mechanisms through which 1C8 and GPS167 affect cancer cell proliferation as well as processes critical for metastasis.”
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28585
Correspondence to: Benoit Chabot
Email: benoit.chabot@usherbrooke.ca
Keywords: CLK kinases inhibitors, EMT, antiviral immune response, microtubules, metastasis
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About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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Aging is contributing at the 2024 Systems Aging Gordon Research Conference in Barcelona, Spain, from June 2–7.
BUFFALO, NY- May 20, 2024 – Aging is a contributor at the 2024 Systems Aging Gordon Research Conference (GRC) on “Systems Modeling, Aging Biomarkers, and Longevity Interventions” — taking place from June 2–7, 2024, in Castelldefels, Barcelona, Spain.
“The conference will present recent advances in systemic rejuvenation, multi-omics approaches, applications ...
The shortage of suitable donor meniscus grafts from the knee and temporomandibular joint (TMJ) impedes treatments for millions of patients. Vitrification offers a promising solution by transitioning these tissues into a vitreous state at cryogenic temperatures, protecting them from ice crystal damage using high concentrations of cryoprotectant agents (CPAs). However, vitrification's success is hindered for larger tissues (>3 mL) due to challenges in CPA penetration. Dense avascular meniscus tissues require extended CPA exposure for adequate penetration; however, ...
CHAMPAIGN, Ill. — By converting their data into sounds, scientists discovered how hydrogen bonds contribute to the lightning-fast gyrations that transform a string of amino acids into a functional, folded protein. Their report, in the Proceedings of the National Academy of Sciences, offers an unprecedented view of the sequence of hydrogen-bonding events that occur when a protein morphs from an unfolded to a folded state.
See video: Protein Sonification
“A protein must fold properly to become an enzyme or signaling molecule or whatever its function may be — all the many things that proteins do in our bodies,” said University of Illinois ...
New York, NY [May 20, 2024]—Researchers at the Icahn School of Medicine at Mount Sinai have designed a regenerative medicine therapy to speed up diabetic wound repair. Using tiny fat particles loaded with genetic instructions to calm down inflammation, the treatment was shown to target problem-causing cells and reduce swelling and harmful molecules in mouse models of damaged skin.
Details on their findings were published in the May 20 online issue of the Proceedings of the National Academy of Sciences (PNAS).
Diabetic wounds, often resistant to conventional treatments, ...
Irvine, Calif., May 20, 2024 — A team of glaciologists led by researchers at the University of California, Irvine used high-resolution satellite radar data to find evidence of the intrusion of warm, high-pressure seawater many kilometers beneath the grounded ice of West Antarctica’s Thwaites Glacier.
In a study published today in Proceedings of the National Academy of Sciences, the UC Irvine-led team said that widespread contact between ocean water and the glacier – a process that is replicated throughout Antarctica and in Greenland – causes “vigorous melting” and may require a reassessment of ...
EMBARGOED UNTIL 15:00 EDT MONDAY, MAY 20, 2024
For the first time, there is visible evidence showing that warm seawater is pumping underneath Antarctica’s Thwaites Glacier—ominously nicknamed the Doomsday Glacier.
An international team of scientists—including a researcher from the University of Waterloo—observed it using satellite imagery and warns that it could accelerate catastrophic sea level rise in 10 to 20 years.
The intrusion of seawater causes the ice to continuously lift off the land and settle back down again. Ice melts intensely when it first touches seawater, ...
Deposits of designated critical minerals needed to transition the world’s energy systems away from fossil fuels may, ironically enough, be co-located with coal deposits that have been mined to produce the fossil fuel most implicated in climate change.
Now, research led by the University of Utah has documented elevated concentrations of a key subset of critical minerals, known as rare earth elements, or REEs, in active mines rimming the Uinta coal belt of Colorado and Utah.
These findings open the possibility that these mines could see a secondary resource stream in the form of metals used in renewable energy and numerous other high-tech ...
EMBARGOED FOR RELEASE: MONDAY, MAY 20, 2024, 3:00 PM ET
Key points:
Replacing an average diesel school bus from 2017 with an electric one may result in $84,200 in health and climate benefits—including fewer greenhouse gas emissions and reduced rates of mortality and childhood asthma—per individual bus.
Those benefits may increase to $247,600 per individual electric school bus replacing a diesel bus from 2005 or earlier in a large metropolitan area.
While the benefits of replacing diesel vehicles with electric ones are well known, this is the first study to specifically quantify the health and climate benefits of replacing diesel school buses with electric ...
Endoscopes are instruments that are used to look inside the body
Even with new developments cleaning them sufficiently has been a challenge
The University has entered a knowledge transfer partnership (KTP) with PFE Medical to improve the process by removing bacterial biofilm inside them.
Aston University experts are teaming up with a medical products company to improve the cleaning of endoscopes.
Endoscopes are long, thin instruments with a light and camera at one end that are used to look inside the body.
Cleaning them sufficiently has been a challenge and even with new developments they can ...
LA JOLLA, CA — The brain is often referred to as a “black box”—one that’s difficult to peer inside and determine what’s happening at any given moment. This is part of the reason why it’s difficult to understand the complex interplay of molecules, cells and genes that underly neurological disorders. But a new CRISPR screen method developed at Scripps Research has the potential to uncover new therapeutic targets and treatments for these conditions.
The method, outlined in a study published in Cell on May 20, 2024, provides a way to rapidly examine the brain cell types ...
