Cargando…
MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability
Osteosarcoma (OS) is the most prevalent human bone malignancy, and presents a global annual morbidity of approximately five cases per million. Notably, precise and efficient targeted therapy has become the most promising strategy for the treatment of OS; however, there is still an urgent need for th...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793648/ https://www.ncbi.nlm.nih.gov/pubmed/33425885 http://dx.doi.org/10.3389/fcell.2020.00825 |
_version_ | 1783634032121085952 |
---|---|
author | Wen, Jia Xie, Yi Zhang, Yingqiang Li, Jiazhen Li, Jiaping Zhang, Yan Lu, Xinchang Zhang, Yi Liu, Yongkui Liu, Tao Li, Longqing |
author_facet | Wen, Jia Xie, Yi Zhang, Yingqiang Li, Jiazhen Li, Jiaping Zhang, Yan Lu, Xinchang Zhang, Yi Liu, Yongkui Liu, Tao Li, Longqing |
author_sort | Wen, Jia |
collection | PubMed |
description | Osteosarcoma (OS) is the most prevalent human bone malignancy, and presents a global annual morbidity of approximately five cases per million. Notably, precise and efficient targeted therapy has become the most promising strategy for the treatment of OS; however, there is still an urgent need for the identification of suitable therapeutic targets. Metastasis-associated in colon cancer 1 (MACC1) was first identified in colon tumors by differential display RT-PCR, and was shown to be involved in the regulation of colon tumor growth and metastasis through the hepatocyte growth factor (HGF)/c-Met signaling pathway. Additionally, MACC1 overexpression has been reported to induce the growth of several types of cancers, including glioblastoma multiforme and gastric cancer. However, whether MACC1 also plays a role in the progression of OS remains unclear. In this study, we found that MACC1 was highly expressed in human OS tissues, as well as in U-2OS and MG-63 cells, when compared with normal tissues and osteoblasts, respectively. Our data further indicated that MACC1 expression was correlated with several clinicopathological features of OS. Through in vitro assays, we found that MACC1 depletion markedly suppressed the proliferative ability of both OS cells and endothelial cells, and inhibited the angiogenic capacity of endothelial cells. Similarly, MACC1 depletion inhibited tumor growth, metastasis, and angiogenesis in mice. Mechanistically, we found that MACC1 could bind to the MET promoter, and enhanced the proliferation of both OS cells and endothelial cells through the HGF/c-Met signaling pathway. Furthermore, we show that MACC1 also promoted angiogenesis by regulating microtubule dynamics, thereby promoting the progression of OS. Our results indicate that MACC1 may be a new and promising therapeutic target for the treatment of OS. |
format | Online Article Text |
id | pubmed-7793648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77936482021-01-09 MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability Wen, Jia Xie, Yi Zhang, Yingqiang Li, Jiazhen Li, Jiaping Zhang, Yan Lu, Xinchang Zhang, Yi Liu, Yongkui Liu, Tao Li, Longqing Front Cell Dev Biol Cell and Developmental Biology Osteosarcoma (OS) is the most prevalent human bone malignancy, and presents a global annual morbidity of approximately five cases per million. Notably, precise and efficient targeted therapy has become the most promising strategy for the treatment of OS; however, there is still an urgent need for the identification of suitable therapeutic targets. Metastasis-associated in colon cancer 1 (MACC1) was first identified in colon tumors by differential display RT-PCR, and was shown to be involved in the regulation of colon tumor growth and metastasis through the hepatocyte growth factor (HGF)/c-Met signaling pathway. Additionally, MACC1 overexpression has been reported to induce the growth of several types of cancers, including glioblastoma multiforme and gastric cancer. However, whether MACC1 also plays a role in the progression of OS remains unclear. In this study, we found that MACC1 was highly expressed in human OS tissues, as well as in U-2OS and MG-63 cells, when compared with normal tissues and osteoblasts, respectively. Our data further indicated that MACC1 expression was correlated with several clinicopathological features of OS. Through in vitro assays, we found that MACC1 depletion markedly suppressed the proliferative ability of both OS cells and endothelial cells, and inhibited the angiogenic capacity of endothelial cells. Similarly, MACC1 depletion inhibited tumor growth, metastasis, and angiogenesis in mice. Mechanistically, we found that MACC1 could bind to the MET promoter, and enhanced the proliferation of both OS cells and endothelial cells through the HGF/c-Met signaling pathway. Furthermore, we show that MACC1 also promoted angiogenesis by regulating microtubule dynamics, thereby promoting the progression of OS. Our results indicate that MACC1 may be a new and promising therapeutic target for the treatment of OS. Frontiers Media S.A. 2020-12-23 /pmc/articles/PMC7793648/ /pubmed/33425885 http://dx.doi.org/10.3389/fcell.2020.00825 Text en Copyright © 2020 Wen, Xie, Zhang, Li, Li, Zhang, Lu, Zhang, Liu, Liu and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Wen, Jia Xie, Yi Zhang, Yingqiang Li, Jiazhen Li, Jiaping Zhang, Yan Lu, Xinchang Zhang, Yi Liu, Yongkui Liu, Tao Li, Longqing MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability |
title | MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability |
title_full | MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability |
title_fullStr | MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability |
title_full_unstemmed | MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability |
title_short | MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability |
title_sort | macc1 contributes to the development of osteosarcoma through regulation of the hgf/c-met pathway and microtubule stability |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793648/ https://www.ncbi.nlm.nih.gov/pubmed/33425885 http://dx.doi.org/10.3389/fcell.2020.00825 |
work_keys_str_mv | AT wenjia macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT xieyi macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT zhangyingqiang macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT lijiazhen macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT lijiaping macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT zhangyan macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT luxinchang macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT zhangyi macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT liuyongkui macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT liutao macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability AT lilongqing macc1contributestothedevelopmentofosteosarcomathroughregulationofthehgfcmetpathwayandmicrotubulestability |