| Форма представления | Статьи в зарубежных журналах и сборниках |
| Год публикации | 2022 |
| Язык | английский |
|
Денека Александр Ярославович, автор
Тихомирова Мария Владимировна, автор
Топчу Юлия Алексеевна, автор
|
|
Бармин Виталий , автор
Ратнер Екатерина Юрьевна, автор
Сабиров Алнксей , автор
|
|
Мазитова Александра Маратовна, автор
|
| Библиографическое описание на языке оригинала |
Tikhomirova M. NEDD9 restrains dsDNA damage eesponse during non-small cell lung cancer (NSCLC) progression / M. Tikhomirova, I. Topchu, A. Mazitova, V. Barmin, E. Ratner, A. Sabirov, Z. Abramova, A. Y. Deneka // Cancers (Basel).- 2022.- V.14, N.10,-:2517 doi: 10.3390/cancers14102517 |
| Аннотация |
DNA damaging modalities are the backbone of treatments for non-small cell lung cancer
(NSCLC). Alterations in DNA damage response (DDR) in tumor cells commonly contribute to
emerging resistance to platinating agents, other targeted therapies, and radiation. The goal of this
study is to identify the previously unreported role of NEDD9 scaffolding protein in controlling DDR
processes and sensitivity to DNA damaging therapies. Using a siRNA-mediated approach to deplete
NEDD9 in a group of human and murine KRAS/TP53-mutant NSCLC cell lines, coupled with a set of
cell viability and clonogenic assays, flow cytometry analysis, and Western blotting, we evaluated the
effects of NEDD9 silencing on cellular proliferation, DDR and epithelial-to-mesenchymal transition
(EMT) signaling, cell cycle, and sensitivity to cisplatin and UV irradiation. Using publicly available
NSCLC datasets (TCGA) and an independent cohort of primary NSCLC tumors, subsequent in silico
and immunohistochemical (IHC) analyses were performed to assess relevant changes in NEDD9
RNA and protein expression across different stages of NSCLC. The results of our study demonstrate
that NEDD9 depletion is associated with the increased tumorigenic capacity of NSCLC cells. These
phenotypes were accompanied by significantly upregulated ATM-CHK2 signaling, shifting towards
a more mesenchymal phenotype in NEDD9 depleted cells and elevated sensitivity to UV-irradiation.
IHC analyses revealed an association between reduced NEDD9 protein expression and a decrease
in overall (OS) and progression-free survival (PFS) of the NSCLC patients. These data, for the first
time, identified NEDD9 as a negative regulator of ATM kinase activity and related DDR signaling in
numerous KRAS/TP53 mutated NSCLC, with its effects on the regulation of DDR-dependent EMT
signaling, sensitivity to DNA damaging modalities in tumor cells, and the survival of the patients. |
| Ключевые слова |
HEF1, DNA damage response,CHK2, ERCC4, non-small cell lung cancer, overall survival |
| Название журнала |
Cancers
|
| URL |
https://pubmed.ncbi.nlm.nih.gov/35626121/ |
| Пожалуйста, используйте этот идентификатор, чтобы цитировать или ссылаться на эту карточку |
https://repository.kpfu.ru/?p_id=267293 |
| Файлы ресурса | |
|
|
Полная запись метаданных  |
| Поле DC |
Значение |
Язык |
| dc.contributor.author |
Денека Александр Ярославович |
ru_RU |
| dc.contributor.author |
Тихомирова Мария Владимировна |
ru_RU |
| dc.contributor.author |
Топчу Юлия Алексеевна |
ru_RU |
| dc.contributor.author |
Бармин Виталий |
ru_RU |
| dc.contributor.author |
Ратнер Екатерина Юрьевна |
ru_RU |
| dc.contributor.author |
Сабиров Алнксей |
ru_RU |
| dc.contributor.author |
Мазитова Александра Маратовна |
ru_RU |
| dc.date.accessioned |
2022-01-01T00:00:00Z |
ru_RU |
| dc.date.available |
2022-01-01T00:00:00Z |
ru_RU |
| dc.date.issued |
2022 |
ru_RU |
| dc.identifier.citation |
Tikhomirova M. NEDD9 restrains dsDNA damage eesponse during non-small cell lung cancer (NSCLC) progression / M. Tikhomirova, I. Topchu, A. Mazitova, V. Barmin, E. Ratner, A. Sabirov, Z. Abramova, A. Y. Deneka // Cancers (Basel).- 2022.- V.14, N.10,-:2517 doi: 10.3390/cancers14102517 |
ru_RU |
| dc.identifier.uri |
https://repository.kpfu.ru/?p_id=267293 |
ru_RU |
| dc.description.abstract |
Cancers |
ru_RU |
| dc.description.abstract |
DNA damaging modalities are the backbone of treatments for non-small cell lung cancer
(NSCLC). Alterations in DNA damage response (DDR) in tumor cells commonly contribute to
emerging resistance to platinating agents, other targeted therapies, and radiation. The goal of this
study is to identify the previously unreported role of NEDD9 scaffolding protein in controlling DDR
processes and sensitivity to DNA damaging therapies. Using a siRNA-mediated approach to deplete
NEDD9 in a group of human and murine KRAS/TP53-mutant NSCLC cell lines, coupled with a set of
cell viability and clonogenic assays, flow cytometry analysis, and Western blotting, we evaluated the
effects of NEDD9 silencing on cellular proliferation, DDR and epithelial-to-mesenchymal transition
(EMT) signaling, cell cycle, and sensitivity to cisplatin and UV irradiation. Using publicly available
NSCLC datasets (TCGA) and an independent cohort of primary NSCLC tumors, subsequent in silico
and immunohistochemical (IHC) analyses were performed to assess relevant changes in NEDD9
RNA and protein expression across different stages of NSCLC. The results of our study demonstrate
that NEDD9 depletion is associated with the increased tumorigenic capacity of NSCLC cells. These
phenotypes were accompanied by significantly upregulated ATM-CHK2 signaling, shifting towards
a more mesenchymal phenotype in NEDD9 depleted cells and elevated sensitivity to UV-irradiation.
IHC analyses revealed an association between reduced NEDD9 protein expression and a decrease
in overall (OS) and progression-free survival (PFS) of the NSCLC patients. These data, for the first
time, identified NEDD9 as a negative regulator of ATM kinase activity and related DDR signaling in
numerous KRAS/TP53 mutated NSCLC, with its effects on the regulation of DDR-dependent EMT
signaling, sensitivity to DNA damaging modalities in tumor cells, and the survival of the patients. |
ru_RU |
| dc.language.iso |
ru |
ru_RU |
| dc.subject |
HEF1 |
ru_RU |
| dc.subject |
DNA damage response |
ru_RU |
| dc.subject |
CHK2 |
ru_RU |
| dc.subject |
ERCC4 |
ru_RU |
| dc.subject |
non-small cell lung cancer |
ru_RU |
| dc.subject |
overall survival |
ru_RU |
| dc.title |
NEDD9 Restrains dsDNA Damage Response during Non-Small Cell Lung Cancer (NSCLC) Progression |
ru_RU |
| dc.type |
Статьи в зарубежных журналах и сборниках |
ru_RU |
|
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