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Title: Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation

Abstract

Research highlights: {yields} Activation of Lymphocyte-specific protein tyrosine kinase (LCK) is involved in the fractionated radiation-induced expansion of glioma stem-like cells. {yields} Inhibition of LCK prevents acquisition of fractionated radiation-induced resistance to chemotherapeutic treatment. {yields} LCK activity is critical for the maintenance of self-renewal in glioma stem-like cells. -- Abstract: Brain cancers frequently recur or progress as focal masses after treatment with ionizing radiation. Radiation used to target gliomas may expand the cancer stem cell population and enhance the aggressiveness of tumors; however, the mechanisms underlying the expansion of cancer stem cell population after radiation have remained unclear. In this study, we show that LCK (lymphocyte-specific protein tyrosine kinase) is involved in the fractionated radiation-induced expansion of the glioma-initiating cell population and acquisition of resistance to anticancer treatments. Fractionated radiation caused a selective increase in the activity of LCK, a Src family non-receptor tyrosine kinase. The activities of other Src family kinases Src, Fyn, and Lyn were not significantly increased. Moreover, knockdown of LCK expression with a specific small interfering RNA (siRNA) effectively blocked fractionated radiation-induced expansion of the CD133{sup +} cell population. siRNA targeting of LCK also suppressed fractionated radiation-induced expression of the glioma stem cell marker proteins CD133,more » Nestin, and Musashi. Expression of the known self-renewal-related proteins Notch2 and Sox2 in glioma cells treated with fractionated radiation was also downregulated by LCK inhibition. Moreover, siRNA-mediated knockdown of LCK effectively restored the sensitivity of glioma cells to cisplatin and etoposide. These results indicate that the non-receptor tyrosine kinase LCK is critically involved in fractionated radiation-induced expansion of the glioma-initiating cell population and decreased cellular sensitivity to anticancer treatments. These findings may provide pivotal insights in the context of fractionated radiation-based therapeutic interventions in brain cancer.« less

Authors:
; ; ;  [1];  [2];  [3];  [1];  [1]
  1. Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)
  2. Functional Genoproteome Research Centre, Konkuk University, Seoul 143-701 (Korea, Republic of)
  3. Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22202902
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 402; Journal Issue: 4; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; GLIOMAS; INHIBITION; LYMPHOCYTES; PHOSPHOTRANSFERASES; RECEPTORS; RNA; SENSITIVITY; STEM CELLS; TYROSINE

Citation Formats

Kim, Rae-Kwon, Yoon, Chang-Hwan, Hyun, Kyung-Hwan, Lee, Hyejin, An, Sungkwan, Park, Myung-Jin, Kim, Min-Jung, and Lee, Su-Jae. Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.10.072.
Kim, Rae-Kwon, Yoon, Chang-Hwan, Hyun, Kyung-Hwan, Lee, Hyejin, An, Sungkwan, Park, Myung-Jin, Kim, Min-Jung, & Lee, Su-Jae. Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation. United States. https://doi.org/10.1016/J.BBRC.2010.10.072
Kim, Rae-Kwon, Yoon, Chang-Hwan, Hyun, Kyung-Hwan, Lee, Hyejin, An, Sungkwan, Park, Myung-Jin, Kim, Min-Jung, and Lee, Su-Jae. Fri . "Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation". United States. https://doi.org/10.1016/J.BBRC.2010.10.072.
@article{osti_22202902,
title = {Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation},
author = {Kim, Rae-Kwon and Yoon, Chang-Hwan and Hyun, Kyung-Hwan and Lee, Hyejin and An, Sungkwan and Park, Myung-Jin and Kim, Min-Jung and Lee, Su-Jae},
abstractNote = {Research highlights: {yields} Activation of Lymphocyte-specific protein tyrosine kinase (LCK) is involved in the fractionated radiation-induced expansion of glioma stem-like cells. {yields} Inhibition of LCK prevents acquisition of fractionated radiation-induced resistance to chemotherapeutic treatment. {yields} LCK activity is critical for the maintenance of self-renewal in glioma stem-like cells. -- Abstract: Brain cancers frequently recur or progress as focal masses after treatment with ionizing radiation. Radiation used to target gliomas may expand the cancer stem cell population and enhance the aggressiveness of tumors; however, the mechanisms underlying the expansion of cancer stem cell population after radiation have remained unclear. In this study, we show that LCK (lymphocyte-specific protein tyrosine kinase) is involved in the fractionated radiation-induced expansion of the glioma-initiating cell population and acquisition of resistance to anticancer treatments. Fractionated radiation caused a selective increase in the activity of LCK, a Src family non-receptor tyrosine kinase. The activities of other Src family kinases Src, Fyn, and Lyn were not significantly increased. Moreover, knockdown of LCK expression with a specific small interfering RNA (siRNA) effectively blocked fractionated radiation-induced expansion of the CD133{sup +} cell population. siRNA targeting of LCK also suppressed fractionated radiation-induced expression of the glioma stem cell marker proteins CD133, Nestin, and Musashi. Expression of the known self-renewal-related proteins Notch2 and Sox2 in glioma cells treated with fractionated radiation was also downregulated by LCK inhibition. Moreover, siRNA-mediated knockdown of LCK effectively restored the sensitivity of glioma cells to cisplatin and etoposide. These results indicate that the non-receptor tyrosine kinase LCK is critically involved in fractionated radiation-induced expansion of the glioma-initiating cell population and decreased cellular sensitivity to anticancer treatments. These findings may provide pivotal insights in the context of fractionated radiation-based therapeutic interventions in brain cancer.},
doi = {10.1016/J.BBRC.2010.10.072},
url = {https://www.osti.gov/biblio/22202902}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 402,
place = {United States},
year = {2010},
month = {11}
}