Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

Seiichiro Ishihara; Motoaki Yasuda; Akihiro Ishizu; Masayori Ishikawa; Hiroki Shirato; Hisashi Haga

doi:10.18632/oncotarget.2912

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Priority Research Papers:

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

Seiichiro Ishihara _, Motoaki Yasuda, Akihiro Ishizu, Masayori Ishikawa, Hiroki Shirato and Hisashi Haga

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Oncotarget. 2015; 6:4602-4614. https://doi.org/10.18632/oncotarget.2912

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Abstract

Seiichiro Ishihara1,2, Motoaki Yasuda3, Akihiro Ishizu4, Masayori Ishikawa5, Hiroki Shirato6, Hisashi Haga1,2

1Faculty of Advanced Life Science, Hokkaido University, Kita-ku, Sapporo 060–0810, Japan

2Research Center for Cooperative Projects, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060–8638, Japan

3Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Kita-ku, Sapporo 060–8586, Japan

4Division of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Kita-ku, Sapporo 060–0812, Japan

5Department of Medical Physics, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060–8638, Japan

6Department of Radiology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060–8638, Japan

Correspondence to:

Hisashi Haga, e-mail: [email protected]

Keywords: Activating transcription factor 5, radioresistance, cell growth, cell invasion, cancer cells

Received: November 04, 2014 Accepted: December 11, 2014 Published: February 17, 2015

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.

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PII: 2912

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Priority Research Papers:

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

Abstract