Mesencephalic astrocyte-derived neurotrophic factor is a novel radioresistance factor in mouse B16 melanoma

被引：3

作者：

Tanaka, Yuta ^{[1
]}

Takenouchi, Takato ^{[2
]}

Tsukimoto, Mitsutoshi ^{[1
]}

机构：

[1] Tokyo Univ Sci, Fac Pharmaceut Sci, Dept Radiat Biosci, 2641 Yamazaki, Noda, Chiba 2780022, Japan

[2] Natl Agr & Food Res Org, Div Anim Sci, Inst Agrobiol Sci, 1-2 Ohwashi, Tsukuba, Ibaraki 3058634, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 524卷 / 04期

关键词：

MANF; Melanoma; Radioresistance; DNA repair; Radiation therapy; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ER STRESS; ISCHEMIA; MANF; PROLIFERATION; SURVIVAL; PATHWAY; ARMET; DEATH;

D O I：

10.1016/j.bbrc.2020.01.167

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neuroprotective factor produced in response to endoplasmic reticulum (ER) stress induced by various stressors, but its involvement in the radioresistance of tumor cells is unknown. Here, we found that MANF is released after gamma-irradiation (2 Gy and 4 Gy) of B16 melanoma cells, and its release was suppressed by 4-phenylbutyric acid, an ER stress inhibitor. MANF was not released after low-dose (1 Gy) gamma-irradiation, but pretreatment of 1 Gy-irradiated cells with recombinant MANF enhanced the cellular DNA damage response and attenuated reproductive cell death. In MANF-knockdown cells, the DNA damage response and p53 activation by gamma-irradiation (2 Gy) were suppressed, and reproductive cell death was increased. MANF also activated the ERK signaling pathway. Our findings raise the possibility that MANF could be a new target for overcoming radioresistance. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：869 / 875

页数：7

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