Nerve growth factor promotes lysyl oxidase-dependent chondrosarcoma cell metastasis by suppressing miR-149-5p synthesis

Huey En Tzeng, Syuan Ling Lin, Louis Anoop Thadevoos, Ming Yu Lien, Wei Hung Yang, Chih Yuan Ko, Chih Yang Lin, Yu Wen Huang, Ju Fang Liu, Yi Chin Fong, Hsien Te Chen, Chih Hsin Tang

研究成果: 雜誌貢獻文章同行評審

摘要

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.

原文英語
文章編號1101
期刊Cell Death and Disease
12
發行號12
DOIs
出版狀態已發佈 - 12月 2021

ASJC Scopus subject areas

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究

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