Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78541, USA.
Int J Mol Sci. 2018 Apr 4;19(4):1078. doi: 10.3390/ijms19041078.
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.
糖基磷脂酰肌醇连接的 GDNF（胶质细胞源性神经营养因子）受体 alpha（GFRA）是一种识别 GDNF 家族配体的核心受体，在神经系统的发育和维持中起着至关重要的作用。在四种已鉴定的 GFRA 同工型中，GFRA1 特异性识别 GDNF，并参与神经元细胞的增殖、分化和迁移的调节。GFRA1 也与癌细胞的进展和转移有关。最近的研究结果表明，GFRA1 可能有助于骨肉瘤中化疗耐药的发展。骨肉瘤细胞用流行的抗癌药物顺铂处理后，GFRA1 的表达被诱导，GFRA1 表达的诱导显著抑制了骨肉瘤细胞中顺铂介导的细胞凋亡。在顺铂处理后，GFRA1 通过激活 SRC-AMPK 信号轴促进自噬，从而导致骨肉瘤细胞存活能力增强。GFRA1 诱导的自噬促进了小鼠异种移植模型中的肿瘤生长，这表明 GFRA1 在骨肉瘤化疗耐药中具有新的功能。
