title: Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin.
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.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Sungjin
authors.initials: S
authors.lastname: Park
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Choong-Man
authors.initials: CM
authors.lastname: Hong
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000528:radiation effects; D000071186:Beclin-1; D045744:Cell Line, Tumor; D005720:Gamma Rays; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000235:genetics; D011836:Radiation Tolerance
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D053495:Osteopontin