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Background <p>Osteosarcoma (OS) is a primary bone malignancy characterized by early metastasis and generally poor prognosis. ESPN is highly expressed and plays an important role in regulating the aggressive phenotypes of several cancer cell types. However, little is known about the molecular mechanisms underlying ESPN-mediated migration and invasion in OS cells.</p> Methods <p>In this study, we first analyzed the survival of osteosarcoma patients using Kaplan-Meier analysis to assess the prognostic relevance of ESPN. To further evaluate its clinical significance, we performed immunohistochemical analysis on osteosarcoma tissue samples and benign osteochondroma (OC) tissues. The biological function of ESPN in osteosarcoma was confirmed by a series of experiments conducted both in vitro and in vivo. Additionally, we explored the underlying molecular mechanisms through Western blotting, co-immunoprecipitation, immunofluorescence, and PCR, revealing key downstream signaling pathways.</p> Results <p>In this study, we demonstrate that ESPN, acting as an oncogene, is highly expressed in OS cell lines and tissues, promoting OS cell proliferation and metastasis. Mechanistically, ESPN promoted the phosphorylation of PI3K by direct interaction with it and active the AKT/mTOR pathway, which enhanced the expression of the transcription factor ZEB1 and initiating the epithelial-mesenchymal transition (EMT) cascade. Furthermore, we validated that mTOR-mediated activation of p70 ribosomal protein S6 kinase (p70S6K) promotes the translation of ZEB1, thereby enhancing the growth and motility of OS cells.</p> Conclusions <p>Our findings reveal a previously unrecognized function of ESPN in OS, closely linked with EMT and cancer metastasis progression. Targeting ESPN may represent a potential therapeutic approach for patients with OS.</p>

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ESPN activates ZEB1-mediated EMT through the PI3K/AKT/mTOR axis to promote osteosarcoma metastasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月9日

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  • Ruikai Zhou,
  • Hongyu Wu,
  • Hao You,
  • Xiaofei Wang,
  • Xiuchen Yuan,
  • Zhengyi Sun,
  • Dong Zhou,
  • Yuqing Jiang,
  • Yifei Shen

摘要

Background

Osteosarcoma (OS) is a primary bone malignancy characterized by early metastasis and generally poor prognosis. ESPN is highly expressed and plays an important role in regulating the aggressive phenotypes of several cancer cell types. However, little is known about the molecular mechanisms underlying ESPN-mediated migration and invasion in OS cells.

Methods

In this study, we first analyzed the survival of osteosarcoma patients using Kaplan-Meier analysis to assess the prognostic relevance of ESPN. To further evaluate its clinical significance, we performed immunohistochemical analysis on osteosarcoma tissue samples and benign osteochondroma (OC) tissues. The biological function of ESPN in osteosarcoma was confirmed by a series of experiments conducted both in vitro and in vivo. Additionally, we explored the underlying molecular mechanisms through Western blotting, co-immunoprecipitation, immunofluorescence, and PCR, revealing key downstream signaling pathways.

Results

In this study, we demonstrate that ESPN, acting as an oncogene, is highly expressed in OS cell lines and tissues, promoting OS cell proliferation and metastasis. Mechanistically, ESPN promoted the phosphorylation of PI3K by direct interaction with it and active the AKT/mTOR pathway, which enhanced the expression of the transcription factor ZEB1 and initiating the epithelial-mesenchymal transition (EMT) cascade. Furthermore, we validated that mTOR-mediated activation of p70 ribosomal protein S6 kinase (p70S6K) promotes the translation of ZEB1, thereby enhancing the growth and motility of OS cells.

Conclusions

Our findings reveal a previously unrecognized function of ESPN in OS, closely linked with EMT and cancer metastasis progression. Targeting ESPN may represent a potential therapeutic approach for patients with OS.