Tristetraprolin affects invasion-associated genes expression and cell motility in triple-negative breast cancer model
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
Akademie Věd České Republiky
RVO68378050
Ustav molekularni genetiky, Akademie Ved Ceske Republiky
CZ.02.01.01/00/22_008/0004562
European Regional Development Fund
RRFU-22-22
Czech Academy of Sciences
05/RISK/EO/22
Czech Academy of Sciences
StrategyAV21(VP29)
Akademie Ved Ceske Republiky
24-11357S
Grant Agency of the Czech Republic
PubMed
39319680
PubMed Central
PMC12063522
DOI
10.1002/cm.21934
Knihovny.cz E-zdroje
- Klíčová slova
- breast cancer, doxorubicin, invasion, motility, tristetraprolin,
- MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- pohyb buněk * genetika účinky léků MeSH
- regulace genové exprese u nádorů * MeSH
- triple-negativní karcinom prsu * genetika patologie metabolismus MeSH
- tristetraprolin * metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- tristetraprolin * MeSH
Tristetraprolin (TTP) is an RNA-binding protein that negatively regulates its target mRNAs and has been shown to inhibit tumor progression and invasion. Tumor invasion requires precise regulation of cytoskeletal components, and dysregulation of cytoskeleton-associated genes can significantly alter cell motility and invasive capability. Several genes, including SH3PXD2A, SH3PXD2B, CTTN, WIPF1, and WASL, are crucial components of the cytoskeleton reorganization machinery and are essential for adequate cell motility. These genes are also involved in invasion processes, with SH3PXD2A, SH3PXD2B, WIPF1, and CTTN being key components of invadopodia-specialized structures that facilitate invasion. However, the regulation of these genes is not well understood. This study demonstrates that ectopic expression of TTP in MDA-MB-231 cells leads to decreased mRNA levels of CTTN and SH3PXD2A, as well as defects in cell motility and actin filament organization. Additionally, doxorubicin significantly increases TTP expression and reduces the mRNA levels of cytoskeleton-associated genes, enhancing our understanding of how doxorubicin may affect the transcriptional profile of cells. However, doxorubicin affects target mRNAs differently than TTP ectopic expression, suggesting it may not be the primary mechanism of doxorubicin in breast cancer (BC) treatment. High TTP expression is considered as a positive prognostic marker in multiple cancers, including BC. Given that doxorubicin is a commonly used drug for treating triple-negative BC, using TTP as a prognostic marker in this cohort of patients might be limited since it might be challenging to understand if high TTP expression occurred due to the favorable physiological state of the patient or as a consequence of treatment.
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