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

doi:10.1038/s41419-021-04392-2

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

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Abstract

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.

Original language	English
Article number	1101
Journal	Cell Death and Disease
Volume	12
Issue number	12
DOIs	https://doi.org/10.1038/s41419-021-04392-2
Publication status	Published - Dec 2021

ASJC Scopus subject areas

Immunology
Cellular and Molecular Neuroscience
Cell Biology
Cancer Research

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41419-021-04392-2

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Tzeng, H. E., Lin, S. L., Thadevoos, L. A., Lien, M. Y., Yang, W. H., Ko, C. Y., Lin, C. Y., Huang, Y. W., Liu, J. F., Fong, Y. C., Chen, H. T., & Tang, C. H. (2021). Nerve growth factor promotes lysyl oxidase-dependent chondrosarcoma cell metastasis by suppressing miR-149-5p synthesis. Cell Death and Disease, 12(12), Article 1101. https://doi.org/10.1038/s41419-021-04392-2

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

abstract = "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.",

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

note = "Funding Information: This work was supported by grants from the Ministry of Science and Technology of Taiwan (MOST 109-2320-B-039-065, MOST 108-2314-B-039-034-MY3), Taipei Medical University, Taiepi (TMU106-AE1-B04), Taipei Medical University Hospital (108TMU-TMUH-24), and China Medical University Hospital, Taichung, Taiwan (DMR-110-017, DMR-110-180, DMR-111-141). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41419-021-04392-2",

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AU - Tzeng, Huey En

AU - Lin, Syuan Ling

AU - Thadevoos, Louis Anoop

AU - Lien, Ming Yu

AU - Yang, Wei Hung

AU - Ko, Chih Yuan

AU - Lin, Chih Yang

AU - Huang, Yu Wen

AU - Liu, Ju Fang

AU - Fong, Yi Chin

AU - Chen, Hsien Te

AU - Tang, Chih Hsin

N1 - Funding Information: This work was supported by grants from the Ministry of Science and Technology of Taiwan (MOST 109-2320-B-039-065, MOST 108-2314-B-039-034-MY3), Taipei Medical University, Taiepi (TMU106-AE1-B04), Taipei Medical University Hospital (108TMU-TMUH-24), and China Medical University Hospital, Taichung, Taiwan (DMR-110-017, DMR-110-180, DMR-111-141). Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

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

Abstract

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