GFRA1: A Novel Molecular Target for the Prevention of Osteosarcoma Chemoresistance.

GFRA1: A Novel Molecular Target for the Prevention of Osteosarcoma Chemoresistance.
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DOI:
10.3390/ijms19041078
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发表时间:
2018-04-04
影响因子:
5.6
通讯作者:
Kim DJ
Kim DJ
中科院分区:
生物学2区
文献类型:
--
作者:
Kim M;Kim DJ

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糖基磷脂酰肌醇连接的胶质细胞源性神经营养因子受体α(GFRA)是一种识别GDNF家族配体的辅助受体,在神经系统的发育和维持中起着至关重要的作用。在已鉴定的四种GFRA亚型中,GFRA1特异性识别GDNF,并参与调节神经细胞的增殖、分化和迁移。GFRA1也与癌细胞的进展和转移有关。最近的研究表明,GFRA1参与了骨肉瘤化疗耐药的发生。常用抗癌药物顺铂诱导骨肉瘤细胞表达GFRA1,并显著抑制顺铂诱导的骨肉瘤细胞凋亡。在顺铂治疗后,GFRA1的表达通过激活SRC-AMPK信号轴促进自噬,从而提高骨肉瘤细胞的存活率。在小鼠异种移植模型中,GFRA1诱导的自噬促进了肿瘤的生长,提示了GFRA1在骨肉瘤化疗耐药中的新功能。
The glycosylphosphatidylinositol-linked GDNF (glial cell derived neurotrophic factor) receptor alpha (GFRA), a coreceptor that recognizes the GDNF family of ligands, has a crucial role in the development and maintenance of the nervous system. Of the four identified GFRA isoforms, GFRA1 specifically recognizes GDNF and is involved in the regulation of proliferation, differentiation, and migration of neuronal cells. GFRA1 has also been implicated in cancer cell progression and metastasis. Recent findings show that GFRA1 can contribute to the development of chemoresistance in osteosarcoma. GFRA1 expression was induced following treatment of osteosarcoma cells with the popular anticancer drug, cisplatin and induction of GFRA1 expression significantly suppressed apoptosis mediated by cisplatin in osteosarcoma cells. GFRA1 expression promotes autophagy by activating the SRC-AMPK signaling axis following cisplatin treatment, resulting in enhanced osteosarcoma cell survival. GFRA1-induced autophagy promoted tumor growth in mouse xenograft models, suggesting a novel function of GFRA1 in osteosarcoma chemoresistance.
DOI: 10.1083/jcb.79.2.371
发表时间: 1978-11
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