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Updated: May 5, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Steroid receptor co-activator-3 promotes osteosarcoma progression through up-regulation of FoxM1
Shuo Geng1, Xiaoyu Wang, Xiaoyan Xu
1Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng St, Nangang, Harbin, Heilongjiang, 150001, China, Geng_Shuo@yeah.net.
Abstract:
Increasing evidence suggests that the three homologous members of steroid receptor co-activator (SRC) family (SRC-1, SRC-2, and SRC-3) play key roles in enhancing cell proliferation in various human cancers, such as breast, prostate, and hepatocellular carcinoma. However, the function of SRC-3 in osteosarcoma remains largely unexplored. In the current study, we found that SRC-3, but not SRC-1 and SRC-2, was dramatically up-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. To explore the functions of SRC-3 in osteosarcoma, in vitro studies were performed in MG63 and U2OS cells. SRC-3 overexpression promoted osteosarcoma cell proliferation, whereas knockdown of SRC-3 inhibits its proliferation. In support of these findings, we further demonstrated that SRC-3 up-regulated FoxM1 expression through co-activation of C/EBPγ. Together our results show that SRC-3 drives osteosarcoma progression and imply it as a therapeutic target to abrogate osteosarcoma.
Insights
Steroid receptor co-activator-3 (SRC-3) promotes osteosarcoma cell growth by up-regulating FoxM1. Targeting SRC-3 may offer a new therapeutic strategy for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Steroid receptor co-activators (SRCs) are implicated in various human cancers.
- The role of SRC-3 in osteosarcoma, a bone cancer, is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of SRC-3 in osteosarcoma progression.
- To determine if SRC-3 is a potential therapeutic target for osteosarcoma.
Main Methods:
- Analysis of SRC-3 expression in human osteosarcoma tissues versus normal tissues.
- In vitro studies using osteosarcoma cell lines (MG63, U2OS) with SRC-3 overexpression and knockdown.
- Investigation of SRC-3's effect on FoxM1 expression and its co-activator C/EBPγ.
Main Results:
- SRC-3 was significantly upregulated in osteosarcoma tissues.
- SRC-3 overexpression enhanced osteosarcoma cell proliferation, while SRC-3 knockdown inhibited it.
- SRC-3 up-regulated FoxM1 expression, mediated by C/EBPγ co-activation.
Conclusions:
- SRC-3 plays a critical role in driving osteosarcoma progression.
- SRC-3 represents a potential therapeutic target for treating osteosarcoma.
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