EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways
Purpose: To investigate the prognostic value and function of six-transmembrane epithelial antigen of prostate 1 (STEAP1) in osteosarcoma and determine whether EFEMP1 mediates its effects. Methods: IHC (immunohistochemistry)/ICC (immunocytochemistry) in conjunction with RT-qPCR (quantitative real-tim...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Bone Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137422000483 |
| _version_ | 1811300276509868032 |
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| author | Dong Zhang Shasha Han Xin Pan Hao Li Hua Zhao Xianlei Gao Songgang Wang |
| author_facet | Dong Zhang Shasha Han Xin Pan Hao Li Hua Zhao Xianlei Gao Songgang Wang |
| author_sort | Dong Zhang |
| collection | DOAJ |
| description | Purpose: To investigate the prognostic value and function of six-transmembrane epithelial antigen of prostate 1 (STEAP1) in osteosarcoma and determine whether EFEMP1 mediates its effects. Methods: IHC (immunohistochemistry)/ICC (immunocytochemistry) in conjunction with RT-qPCR (quantitative real-time polymerase chain reaction) were employed to assess the expression of STEAP1 in paratumoral tissues, osteosarcoma, benign fibrous dysplasia, osteosarcoma cells, normal osteoblastic hFOB cells, as well as various invasive subclones. The association of STEAP1 with outcome was examined with Kaplan–Meier graph among the osteosarcoma population. The effects of the down-regulation and up-regulation of STEAP1 on the biological behavior of osteosarcoma cells were studied through in-vitro and in-vivo functional tests. Results: Up-regulation of STEAP1 in the osteosarcoma tissues, whose correlations with the malignant osteosarcoma phenotype and the poor patient outcome were positive. In addition, STEAP1 induced the epithelial–mesenchymal transition (EMT) via the Wnt/β-catenin and TGF-β/Smad2/3 pathways and facilitated the osteosarcoma cell infiltration and migration. An increase or decrease in EFEMP1 expression directly promoted or inhibited the expression of STEAP1. In osteosarcoma cells overexpressing EFEMP1, STEAP1 knockdown significantly inhibited cell invasion, EMT process, and increased activity of Wnt/β-catenin and TGF-β/Smad2/3 signaling pathways. Although exogenous EFEMP1 could stimulate the Wnt/β-catenin and TGF-β/Smad2/3 pathways to promote the EMT, it had not effect on osteosarcoma cells with STEAP1 knockdown. Collectively, similar to EFEMP1, STEAP1 acted like an oncogene in the osteosarcoma progression. Conclusion: EFEMP1 enabled the Wnt/β-catenin and TGF-β/Smad2/3 axises initiation and EMT elicitation by targeting STEAP1, thereby facilitating the osteosarcoma cell infiltration and migration. These results are expected to contribute to the search for new targeted drugs able to effectively inhibit invasion and metastasis and improve prognosis in osteosarcoma. |
| first_indexed | 2024-04-13T06:48:40Z |
| format | Article |
| id | doaj.art-b325f31fdea14d64b3c380e8e43bd8e5 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-04-13T06:48:40Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-b325f31fdea14d64b3c380e8e43bd8e52022-12-22T02:57:28ZengElsevierJournal of Bone Oncology2212-13742022-12-0137100458EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathwaysDong Zhang0Shasha Han1Xin Pan2Hao Li3Hua Zhao4Xianlei Gao5Songgang Wang6Department of Orthopedics, Suzhou Hospital of Anhui Medical University, Bianhe Zhonglu 229, Suzhou, Anhui 234000, PR ChinaDepartment of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR ChinaDepartment of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR ChinaDepartment of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR ChinaDepartment of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR ChinaDepartment of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR ChinaDepartment of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR China; Corresponding author at: Department of orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xilu 44, Jinan, Shandong 250012, PR China.Purpose: To investigate the prognostic value and function of six-transmembrane epithelial antigen of prostate 1 (STEAP1) in osteosarcoma and determine whether EFEMP1 mediates its effects. Methods: IHC (immunohistochemistry)/ICC (immunocytochemistry) in conjunction with RT-qPCR (quantitative real-time polymerase chain reaction) were employed to assess the expression of STEAP1 in paratumoral tissues, osteosarcoma, benign fibrous dysplasia, osteosarcoma cells, normal osteoblastic hFOB cells, as well as various invasive subclones. The association of STEAP1 with outcome was examined with Kaplan–Meier graph among the osteosarcoma population. The effects of the down-regulation and up-regulation of STEAP1 on the biological behavior of osteosarcoma cells were studied through in-vitro and in-vivo functional tests. Results: Up-regulation of STEAP1 in the osteosarcoma tissues, whose correlations with the malignant osteosarcoma phenotype and the poor patient outcome were positive. In addition, STEAP1 induced the epithelial–mesenchymal transition (EMT) via the Wnt/β-catenin and TGF-β/Smad2/3 pathways and facilitated the osteosarcoma cell infiltration and migration. An increase or decrease in EFEMP1 expression directly promoted or inhibited the expression of STEAP1. In osteosarcoma cells overexpressing EFEMP1, STEAP1 knockdown significantly inhibited cell invasion, EMT process, and increased activity of Wnt/β-catenin and TGF-β/Smad2/3 signaling pathways. Although exogenous EFEMP1 could stimulate the Wnt/β-catenin and TGF-β/Smad2/3 pathways to promote the EMT, it had not effect on osteosarcoma cells with STEAP1 knockdown. Collectively, similar to EFEMP1, STEAP1 acted like an oncogene in the osteosarcoma progression. Conclusion: EFEMP1 enabled the Wnt/β-catenin and TGF-β/Smad2/3 axises initiation and EMT elicitation by targeting STEAP1, thereby facilitating the osteosarcoma cell infiltration and migration. These results are expected to contribute to the search for new targeted drugs able to effectively inhibit invasion and metastasis and improve prognosis in osteosarcoma.http://www.sciencedirect.com/science/article/pii/S2212137422000483STEAP1OsteosarcomaWnt/β-catenin signal pathwayTGF-β/Smad2/3 axisEMTInvasion |
| spellingShingle | Dong Zhang Shasha Han Xin Pan Hao Li Hua Zhao Xianlei Gao Songgang Wang EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways Journal of Bone Oncology STEAP1 Osteosarcoma Wnt/β-catenin signal pathway TGF-β/Smad2/3 axis EMT Invasion |
| title | EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways |
| title_full | EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways |
| title_fullStr | EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways |
| title_full_unstemmed | EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways |
| title_short | EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways |
| title_sort | efemp1 binds to steap1 to promote osteosarcoma proliferation and invasion via the wnt β catenin and tgf β smad2 3 signal pathways |
| topic | STEAP1 Osteosarcoma Wnt/β-catenin signal pathway TGF-β/Smad2/3 axis EMT Invasion |
| url | http://www.sciencedirect.com/science/article/pii/S2212137422000483 |
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