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Background <p><i>SPRY1</i> from the Sprouty family is frequently overexpressed in many tumors and is accompanied by poor prognosis and metastatic progression. However, its role in the tumorigenesis of Wilms tumor (WT) remains unknown. The aim of this study is to elucidate the functional role of <i>SPRY1</i> in the oncogenesis of Wilms tumor.</p> Materials and Methods <p>Public datasets and clinical WT samples were collected to evaluate the expression and clinical significance of <i>SPRY1</i> in patients with WT. Chip-qPCR, CCK8, transwell assays, wound-healing assay, immunohistochemistry (IHC), immunofluorescence, and a subcutaneous xenograft tumor model were utilized to examine the biological function of <i>SPRY1</i>. Biogrid prediction, coimmunoprecipitation (Co-IP), and functional gains and loss experiments revealed the downstream regulatory mechanism of <i>SPRY1</i>.</p> Results <p>We showed that high expression of <i>SPRY1</i> was associated with poor prognosis of patients with Wilms tumor in public datasets, which was verified by cell lines. <i>SPRY1</i> knockdown significantly inhibited cellular proliferation, migration, and invasion both in vitro and in vivo. The E3 ubiquitin ligase<i>CBL</i> was identified as a target protein that interacts with <i>SPRY1</i> with the aid of the Biogrid database. Mechanistically, <i>SPRY1</i> disrupted <i>CBL</i>–<i>vimentin</i> binding by competing with <i>vimentin</i> for binding to <i>CBL</i> in an enzyme-independent manner. Upregulation of<i> SPRY1</i> increases combination with <i>CBL</i>, reducing <i>vimentin</i> ubiquitination by <i>CBL</i> and promoting <i>vimentin</i> accumulation.</p> Conclusions <p>Collectively, these findings indicate that the accumulation of <i>SPRY1</i> led to stabilization of <i>vimentin</i> by binding to <i>CBL</i>, thus resulting in hyperactivation of the EMT pathway to promote carcinogenesis in Wilms tumor. This provides a potential strategy to treat Wilms tumor targeting the <i>SPRY1</i>–<i>CBL</i>–<i>vimentin </i>axis.</p>

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SPRY1 Interaction with CBL Promotes Vimentin Stabilization to Enhance Malignant Progression and Metastasis in Wilms Tumor

  • 期刊论文

  • 发表日期：

    2025年9月1日

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  • Fan Huang,
  • Hongjie Gao,
  • Zhiyi Lu,
  • Yanping Wang,
  • Ding Li,
  • Xuetian Li,
  • Fengyin Sun

摘要

Background

SPRY1 from the Sprouty family is frequently overexpressed in many tumors and is accompanied by poor prognosis and metastatic progression. However, its role in the tumorigenesis of Wilms tumor (WT) remains unknown. The aim of this study is to elucidate the functional role of SPRY1 in the oncogenesis of Wilms tumor.

Materials and Methods

Public datasets and clinical WT samples were collected to evaluate the expression and clinical significance of SPRY1 in patients with WT. Chip-qPCR, CCK8, transwell assays, wound-healing assay, immunohistochemistry (IHC), immunofluorescence, and a subcutaneous xenograft tumor model were utilized to examine the biological function of SPRY1. Biogrid prediction, coimmunoprecipitation (Co-IP), and functional gains and loss experiments revealed the downstream regulatory mechanism of SPRY1.

Results

We showed that high expression of SPRY1 was associated with poor prognosis of patients with Wilms tumor in public datasets, which was verified by cell lines. SPRY1 knockdown significantly inhibited cellular proliferation, migration, and invasion both in vitro and in vivo. The E3 ubiquitin ligaseCBL was identified as a target protein that interacts with SPRY1 with the aid of the Biogrid database. Mechanistically, SPRY1 disrupted CBL–vimentin binding by competing with vimentin for binding to CBL in an enzyme-independent manner. Upregulation of SPRY1 increases combination with CBL, reducing vimentin ubiquitination by CBL and promoting vimentin accumulation.

Conclusions

Collectively, these findings indicate that the accumulation of SPRY1 led to stabilization of vimentin by binding to CBL, thus resulting in hyperactivation of the EMT pathway to promote carcinogenesis in Wilms tumor. This provides a potential strategy to treat Wilms tumor targeting the SPRY1–CBL–vimentin axis.