title: Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells.
abstract: Radiotherapy is effective for treating various types of tumors. However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes that correlate with poor prognosis. It is not known how cancer cells survive and generate malignant tumors after irradiation. Here, we show that activating transcription factor 5 (ATF5) promotes radioresistance and malignancy in cancer cells after irradiation. In the G1-S phase of the cell cycle, cancer cells express high levels of ATF5, which promotes cell cycle progression and thereby increases radioresistance. Furthermore, ATF5 increases malignant phenotypes, such as cell growth and invasiveness, in cancer cells in vitro and in vivo. We have identified a new mechanism for the regeneration of highly malignant tumors after irradiation and shown that ATF5 plays a key role in the process.
authors: Faculty of Advanced Life Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.|Research Center for Cooperative Projects, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan.
authors: Seiichiro
authors: S
authors: Ishihara
authors: Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Kita-ku, Sapporo 060-8586, Japan.
authors: Motoaki
authors: M
authors: Yasuda
authors: Division of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors: Akihiro
authors: A
authors: Ishizu
authors: Department of Medical Physics, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan.
authors: Masayori
authors: M
authors: Ishikawa
authors: Department of Radiology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan.
authors: Hiroki
authors: H
authors: Shirato
authors: Faculty of Advanced Life Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.|Research Center for Cooperative Projects, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan.
authors: Hisashi
authors: H
authors: Haga
mesh_terms: D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C507532:ATF5 protein, human; D051696:Activating Transcription Factors; D012333:RNA, Messenger
keywords: activating transcription factor 5; cancer cells; cell growth; cell invasion; radioresistance