Induction of HSP27 and HSP70 by constitutive overexpression of Redd1 confers resistance of lung cancer cells 
to ionizing radiation

Jin,Hyeon‑Ok; Hong,Sung‑Eun; Kim,Ji‑Young; Kim,Mi‑Ri; Chang,Yoon  Hwan; Hong,Young  Jun; Lee,Jin  Kyung; Park,In‑Chul

doi:10.3892/or.2019.7036

Induction of HSP27 and HSP70 by constitutive overexpression of Redd1 confers resistance of lung cancer cells to ionizing radiation

Authors:
- Hyeon‑Ok Jin
- Sung‑Eun Hong
- Ji‑Young Kim
- Mi‑Ri Kim
- Yoon Hwan Chang
- Young Jun Hong
- Jin Kyung Lee
- In‑Chul Park
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Affiliations: KIRAMS Radiation Biobank, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Division of Basic Radiation Bioscience, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
Published online on: February 28, 2019 https://doi.org/10.3892/or.2019.7036
Pages: 3119-3126

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Abstract

Redd1 is a stress response protein that functions as a repressor of mTORC1, a central regulator of protein translation, resulting in the inhibition of cell growth and metabolism. However, paradoxically, high Redd1 expression favors cancer progression and generates resistance to cancer therapy. Herein, we revealed that constitutive overexpression of Redd1 induced HSP27 and HSP70 expression in lung cancer cells. The expression of Redd1, HSP27 and HSP70 was highly increased in lung cancer tissues compared with that in normal lung tissues. Inhibition of HSP27 or HSP70 suppressed AKT phosphorylation, which was induced by constitutive overexpression of Redd1 and enhanced the inhibitory effects on viability of Redd1‑overexpressing cells. Inhibition of AKT phosphorylation resulted in a decrease of HSP27 and HSP70 expression in Redd1‑overexpressing cells. These data indicated that HSPs and AKT in Redd1‑overexpressing cells positively regulated the function and expression of each other and were involved in lung cancer cell survival. Knockdown of HSP27, HSP70 or AKT enhanced ionizing radiation (IR) sensitivity, particularly in lung cancer cells in which Redd1 was stably overexpressed. Collectively, constitutive overexpression of Redd1 led to HSP27 and HSP70 induction and AKT activation, which were involved in lung cancer cell survival and resistance to IR, suggesting that Redd1 may be used as a therapeutic target for lung cancer.

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