Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Cell Death Dis. 2021 Nov 23;12(12):1101. doi: 10.1038/s41419-021-04392-2.
Chondrosarcoma is a malignancy of soft tissue and bone that has a high propensity to metastasize to distant organs. Nerve growth factor (NGF) is critical for neuronal cell growth, apoptosis, and differentiation, and also appears to promote the progression and metastasis of several different types of tumors, although the effects of NGF upon chondrosarcoma mechanisms are not very clear. We report that NGF facilitates lysyl oxidase (LOX)-dependent cellular migration and invasion in human chondrosarcoma cells, and that NGF overexpression enhances lung metastasis in a mouse model of chondrosarcoma. NGF-induced stimulation of LOX production and cell motility occurs through the inhibition of miR-149-5p expression, which was reversed by PI3K, Akt, and mTOR inhibitors and their respective short interfering RNAs. Notably, levels of NGF and LOX expression correlated with tumor stage in human chondrosarcoma samples. Thus, NGF appears to be a worthwhile therapeutic target for metastatic chondrosarcoma.
软骨肉瘤是一种软组织和骨骼的恶性肿瘤，具有向远处器官转移的高倾向。神经生长因子（NGF）对神经元细胞的生长、凋亡和分化至关重要，它似乎也促进了几种不同类型肿瘤的进展和转移，尽管 NGF 对软骨肉瘤机制的影响尚不清楚。我们报告称，NGF 促进人软骨肉瘤细胞赖氨酰氧化酶（LOX）依赖性细胞迁移和侵袭，并且 NGF 过表达增强了软骨肉瘤小鼠模型中的肺转移。NGF 诱导的 LOX 产生和细胞运动的刺激作用是通过抑制 miR-149-5p 的表达来实现的，而这一过程可以被 PI3K、Akt 和 mTOR 抑制剂及其各自的短发夹 RNA 逆转。值得注意的是，NGF 和 LOX 表达水平与人类软骨肉瘤样本的肿瘤分期相关。因此，NGF 似乎是转移性软骨肉瘤有价值的治疗靶点。
