KFU. Card publication. Nedd9 Regulates Metastasis of Non-Small Cell Lung Cancer through Activation of Epithelial-Mesenchymal Transition and Tumor Cells Migration

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NEDD9 REGULATES METASTASIS OF NON-SMALL CELL LUNG CANCER THROUGH ACTIVATION OF EPITHELIAL-MESENCHYMAL TRANSITION AND TUMOR CELLS MIGRATION

Form of presentation

Articles in international journals and collections

Year of publication

2020

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Authors, employees of KFU

Abramova Zinaida Ivanovna, author

Deneka Aleksandr Yaroslavovich, author

Mazitova Aleksandra Maratovna, author

Tikhomirova Mariya Vladimirovna, author

Topchu Yuliya Alekseevna, author

Bibliographic description in the original language

Topchu Y. A., Mazitova A. M., Tikhomirova M, Nedd9 Regulates Metastasis of Non-Small Cell Lung Cancer through Activation of Epithelial-Mesenchymal Transition and Tumor Cells Migration//UCHENYE ZAPISKI KAZANSKOGO UNIVERSITETA-SERIYA ESTESTVENNYE NAUKI. - 2020. - Vol.162, Is.1. - P.123-133.

Annotation

Non-small cell lung cancer (NSCLC) has a low survival rate, with metastasis contributing to the vast majority of deaths. Elevated expression of the protein Nedd9 (neural precursor cell expressed, developmentally down-regulated 9) has been reported in a large subset of lung cancers and other malignancies as a promotor of aggressive phenotypes and drug resistance. This study was performed to identify the mechanisms by which Nedd9 regulates invasion and metastasis of non-small cell lung cancer in the transgenic murine model. Aiming to address the research goals, we performed a set of in vivo and in vitro experiments with the help of such methods as magnetic resonance imaging (MRI), immunohistochemical staining of tissues and microscopy, western blotting. We found that Nedd9 constitutive null genotype enhanced tumor growth in an inducible Kras/Trp53 model, in which Kras mutation is induced specifically in the lung tissue by inhalation of adenovirus. Pathological examination of the tissues demonstrated that Nedd9 null genotype also was associated with higher invasive capacity in vivo, including direct invasion to the heart. We carried out a set of experiments to unveil the mechanism underlying the phenotype discovered. Overall, our data support the model in which Nedd9 provides critical support for early stages of the NSCLC growth, and progression beyond this early stage in the absence of Nedd9 requires extensive intracellular protein signaling reprogramming, allowing tumor cells to acquire mesenchymal properties, such as increased mobility and invasion due to a compensatory rearrangement of intracellular protein signaling pathways and activation of the epithelial-mesenchymal transition (EMT). These results are novel and have not been reviously described in the literature. The biological mechanism by which Nedd9 regulates growth, invasion, and metastasis of NSCLC has been poorly investigated, and its study carries not only fundamental implication – discovery of novel mechanisms driving tumor development, but also significant practical importance: assessment of levels of Nedd9 activity in NSCLC patients can potentially serve as a biomarker of response to chemotherapy.

Keywords

lung cancer, metastasis, epithelial to mesenchymal transition, immunohistochemistry, transgenic murine model

The name of the journal

UCHENYE ZAPISKI KAZANSKOGO UNIVERSITETA-SERIYA ESTESTVENNYE NAUKI

URL

https://kpfu.ru/uz-eng-ns-2020-1-8.html

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=251775&p_lang=2

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Uchen._zap._Kazan._un_ta._2020_162_1_est_8.pdf	0,66	pdf	show / download

Full metadata record

Field DC	Value	Language
dc.contributor.author	Abramova Zinaida Ivanovna	ru_RU
dc.contributor.author	Deneka Aleksandr Yaroslavovich	ru_RU
dc.contributor.author	Mazitova Aleksandra Maratovna	ru_RU
dc.contributor.author	Tikhomirova Mariya Vladimirovna	ru_RU
dc.contributor.author	Topchu Yuliya Alekseevna	ru_RU
dc.date.accessioned	2020-01-01T00:00:00Z	ru_RU
dc.date.available	2020-01-01T00:00:00Z	ru_RU
dc.date.issued	2020	ru_RU
dc.identifier.citation	Topchu Y. A., Mazitova A. M., Tikhomirova M, Nedd9 Regulates Metastasis of Non-Small Cell Lung Cancer through Activation of Epithelial-Mesenchymal Transition and Tumor Cells Migration//UCHENYE ZAPISKI KAZANSKOGO UNIVERSITETA-SERIYA ESTESTVENNYE NAUKI. - 2020. - Vol.162, Is.1. - P.123-133.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=251775&p_lang=2	ru_RU
dc.description.abstract	UCHENYE ZAPISKI KAZANSKOGO UNIVERSITETA-SERIYA ESTESTVENNYE NAUKI	ru_RU
dc.description.abstract	Non-small cell lung cancer (NSCLC) has a low survival rate, with metastasis contributing to the vast majority of deaths. Elevated expression of the protein Nedd9 (neural precursor cell expressed, developmentally down-regulated 9) has been reported in a large subset of lung cancers and other malignancies as a promotor of aggressive phenotypes and drug resistance. This study was performed to identify the mechanisms by which Nedd9 regulates invasion and metastasis of non-small cell lung cancer in the transgenic murine model. Aiming to address the research goals, we performed a set of in vivo and in vitro experiments with the help of such methods as magnetic resonance imaging (MRI), immunohistochemical staining of tissues and microscopy, western blotting. We found that Nedd9 constitutive null genotype enhanced tumor growth in an inducible Kras/Trp53 model, in which Kras mutation is induced specifically in the lung tissue by inhalation of adenovirus. Pathological examination of the tissues demonstrated that Nedd9 null genotype also was associated with higher invasive capacity in vivo, including direct invasion to the heart. We carried out a set of experiments to unveil the mechanism underlying the phenotype discovered. Overall, our data support the model in which Nedd9 provides critical support for early stages of the NSCLC growth, and progression beyond this early stage in the absence of Nedd9 requires extensive intracellular protein signaling reprogramming, allowing tumor cells to acquire mesenchymal properties, such as increased mobility and invasion due to a compensatory rearrangement of intracellular protein signaling pathways and activation of the epithelial-mesenchymal transition (EMT). These results are novel and have not been reviously described in the literature. The biological mechanism by which Nedd9 regulates growth, invasion, and metastasis of NSCLC has been poorly investigated, and its study carries not only fundamental implication – discovery of novel mechanisms driving tumor development, but also significant practical importance: assessment of levels of Nedd9 activity in NSCLC patients can potentially serve as a biomarker of response to chemotherapy.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	lung cancer	ru_RU
dc.subject	metastasis	ru_RU
dc.subject	epithelial to mesenchymal transition	ru_RU
dc.subject	immunohistochemistry	ru_RU
dc.subject	transgenic murine model	ru_RU
dc.title	Nedd9 Regulates Metastasis of Non-Small Cell Lung Cancer through Activation of Epithelial-Mesenchymal Transition and Tumor Cells Migration	ru_RU
dc.type	Articles in international journals and collections	ru_RU