A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER

Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins,  toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA  damage. On the other hand, autophagy may...

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Main Authors: S. V. Vtorushin, K. V. Rachkovsky, N. V. Krakhmal, I. V. Stepanov, M. V. Zavyalova
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Tomsk National Research Medical Center 2018-09-01
Series:Сибирский онкологический журнал
Subjects:
Online Access:https://www.siboncoj.ru/jour/article/view/814
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author S. V. Vtorushin
K. V. Rachkovsky
N. V. Krakhmal
I. V. Stepanov
M. V. Zavyalova
author_facet S. V. Vtorushin
K. V. Rachkovsky
N. V. Krakhmal
I. V. Stepanov
M. V. Zavyalova
author_sort S. V. Vtorushin
collection DOAJ
description Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins,  toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA  damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and  in the presence of reactive oxygen species, which occurs primarily due to blocking of  apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics.  Autophagy regulation is a complicated and multi-stage process. The main regulator here is a  signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian  target of rapamycin). Data on the impact of autophagic proteins ATG5, LC3A, LC3B, and  Beclin-1 on malignant cell survival as well as on tumor growth and progression have been  reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest.The aim of the study is to investigate a relationship between the expression parameters of  autophagy regulatory proteins m-TOR and Beclin-1 and the features of lymphogenic metastasis in colorectal cancer.Materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of  Tomsk Research Medical Center from 2012 to 2015. The average age of patients was  59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy  samples of primary tumor tissue. Staging of colorectal cancer was determined according to  the TNM classification of malignant tumors (2002).Results. Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and Beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables.Conclusion. The obtained findings clearly exhibit that deceleration or loss of autophagic  activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.
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spelling doaj.art-5686384ef90f4af2b6cfd6809c6f530d2025-03-02T11:16:10ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682018-09-01174414710.21294/1814-4861-2018-17-4-41-47560A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCERS. V. Vtorushin0K. V. Rachkovsky1N. V. Krakhmal2I. V. Stepanov3M. V. Zavyalova4Siberian State Medical UniversitySiberian State Medical UniversitySiberian State Medical UniversitySiberian State Medical UniversitySiberian State Medical UniversityCurrently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins,  toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA  damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and  in the presence of reactive oxygen species, which occurs primarily due to blocking of  apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics.  Autophagy regulation is a complicated and multi-stage process. The main regulator here is a  signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian  target of rapamycin). Data on the impact of autophagic proteins ATG5, LC3A, LC3B, and  Beclin-1 on malignant cell survival as well as on tumor growth and progression have been  reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest.The aim of the study is to investigate a relationship between the expression parameters of  autophagy regulatory proteins m-TOR and Beclin-1 and the features of lymphogenic metastasis in colorectal cancer.Materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of  Tomsk Research Medical Center from 2012 to 2015. The average age of patients was  59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy  samples of primary tumor tissue. Staging of colorectal cancer was determined according to  the TNM classification of malignant tumors (2002).Results. Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and Beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables.Conclusion. The obtained findings clearly exhibit that deceleration or loss of autophagic  activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.https://www.siboncoj.ru/jour/article/view/814colorectal cancerautophagylymphogenous metastasisbeclin-1m-torprognosis
spellingShingle S. V. Vtorushin
K. V. Rachkovsky
N. V. Krakhmal
I. V. Stepanov
M. V. Zavyalova
A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER
Сибирский онкологический журнал
colorectal cancer
autophagy
lymphogenous metastasis
beclin-1
m-tor
prognosis
title A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER
title_full A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER
title_fullStr A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER
title_full_unstemmed A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER
title_short A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER
title_sort link between autophagy regulatory proteins m tor and beclin 1 and parameters of lymphogenic metastasis in colorectal cancer
topic colorectal cancer
autophagy
lymphogenous metastasis
beclin-1
m-tor
prognosis
url https://www.siboncoj.ru/jour/article/view/814
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