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LILRB2 inhibition enhances radiation sensitivity in non-small cell lung cancer by attenuating radiation-induced senescence.
- Source :
-
Cancer letters [Cancer Lett] 2024 Jul 01; Vol. 593, pp. 216930. Date of Electronic Publication: 2024 May 03. - Publication Year :
- 2024
-
Abstract
- Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.<br />Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Cell Line, Tumor
Cell Proliferation radiation effects
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
STAT3 Transcription Factor metabolism
STAT3 Transcription Factor genetics
Animals
Janus Kinase 2 metabolism
Janus Kinase 2 genetics
Mice
Signal Transduction
Gene Expression Regulation, Neoplastic radiation effects
Senescence-Associated Secretory Phenotype genetics
A549 Cells
Female
Carcinoma, Non-Small-Cell Lung radiotherapy
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Non-Small-Cell Lung metabolism
Cellular Senescence radiation effects
Radiation Tolerance genetics
Lung Neoplasms radiotherapy
Lung Neoplasms genetics
Lung Neoplasms pathology
Lung Neoplasms metabolism
Receptors, Immunologic genetics
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 593
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 38705566
- Full Text :
- https://doi.org/10.1016/j.canlet.2024.216930