Beclin1-induced Autophagy Abrogates Radioresistance of Lung Cancer Cells by Suppressing Osteopontin

• Type of Material: Article
• Authors: Seung-Hee Chang, Seoul National University; Arash Minai-Tehrani, Seoul National University; Ji-Young Shin, Seoul National University; Sungjin Park, Seoul National University; Ji-Eun Kim, Seoul National University; Kyeong-Nam Yu, Seoul National University; Seong-Ho Hong, Seoul National University; Choong-Man Hong, Osong Health Technology Administration Complex; Kee-Ho Lee, Korea Institute of Radiological and Medical Sciences; George R Beck Jr, Emory University; Myung-Haing Cho, Seoul National University
• Language: English
• Date: 2012-05-01
• Publisher: Oxford University Press (OUP): Policy C - Option B
• Publication Version: Final Published Version
• Copyright Statement: © The Japan Radiation Research Editorial Committee
• Final Published Version (URL): http://dx.doi.org/10.1269/jrr.11148
• Title of Journal or Parent Work: Journal of Radiation Research
• ISSN: 0449-3060
• Volume: 53
• Issue: 3
• Start Page: 422
• End Page: 432
• Grant/Funding Information: This work was supported by the National Research Foundation (NRF-2012-0000102) of the Ministry of Education, Science and Technology (MEST) in Korea.; M.H. CHO was also partially supported by the Research Institute for Veterinary Science, Seoul National University
• Keywords: Life Sciences & Biomedicine - Other Topics; EXPRESSION; APOPTOSIS; BREAST-CANCER; Beclin-1(BECN1); COLON; PROMOTER; Angiogenesis; TUMOR-GROWTH; Osteopontin(OPN); Gamma-irradiation; METASTASIS; Biology; ENDOTHELIAL GROWTH-FACTOR; Science & Technology; Life Sciences & Biomedicine; Radiology, Nuclear Medicine & Medical Imaging; Oncology; p53; IN-VIVO; GENE
• Research Categories: Health Sciences, Oncology; Health Sciences, Radiology; Health Sciences, Medicine and Surgery

Abstract

Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy.