Targeting proteostasis in multiple myeloma through inhibition of LTK
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00141729" target="_blank" >RIV/00216224:14110/25:00141729 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41375-025-02682-8" target="_blank" >https://www.nature.com/articles/s41375-025-02682-8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41375-025-02682-8" target="_blank" >10.1038/s41375-025-02682-8</a>
Alternative languages
Result language
angličtina
Original language name
Targeting proteostasis in multiple myeloma through inhibition of LTK
Original language description
Multiple myeloma (MM) cells secrete high levels of immunoglobulin and are therefore addicted to mechanisms that maintain proteome homeostasis (proteostasis). While proteasome inhibitors that target the degradative aspect of proteostasis have proven effective, only limited attempts have been made to target protein secretion. Here we show that the receptor tyrosine kinase LTK is a regulatory node in the proteostasis network that responds to secretory load and helps cells maintain a high secretory output. LTK is a highly similar paralog to ALK and by repurposing existing ALK inhibitors, we demonstrate that targeting LTK causes immunoglobulin retention, ER stress and subsequent apoptosis of primary MM cells, even in patients refractory to proteasome inhibitors. Thus, LTK is a novel therapeutic target in the biosynthetic pathway of proteostasis, with significant potential for MM treatment.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia
ISSN
0887-6924
e-ISSN
1476-5551
Volume of the periodical
39
Issue of the periodical within the volume
9
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
2237-2245
UT code for WoS article
001527724200001
EID of the result in the Scopus database
2-s2.0-105010413889