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<p>Melanoma is a highly malignant tumor, with its initiation and progression tightly linked to the aberrant activation of the MAPK signaling pathway. As a critical negative regulator of the MAPK pathway, <i>SPRED1</i> frequently exhibits genomic alteration in melanoma, including gene deletions and mutations, which lead to its functional inactivation. Consequently, the loss of <i>SPRED1</i>-mediated inhibition on the MAPK pathway significantly drives tumorigenesis and progression, enhances invasive and metastatic capacities, and is closely associated with therapeutic resistance. This article systematically reviews the structure and biological functions of <i>SPRED1</i>, its mutation profiles across different melanoma subtypes, and its regulatory mechanisms on the MAPK pathway. Furthermore, it discusses the associations of <i>SPRED1</i> alteration with tumor malignant progression, as well as resistance to targeted therapy and immunotherapy. This review aims to provide a comprehensive theoretical basis for the precise diagnosis, treatment, and fundamental research of melanoma.</p>

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The role of SPRED1 mutation in melanoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月15日

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  • Hui Hou,
  • Jiao Li,
  • Jianxiao Xing,
  • Ruixia Hou

摘要

Melanoma is a highly malignant tumor, with its initiation and progression tightly linked to the aberrant activation of the MAPK signaling pathway. As a critical negative regulator of the MAPK pathway, SPRED1 frequently exhibits genomic alteration in melanoma, including gene deletions and mutations, which lead to its functional inactivation. Consequently, the loss of SPRED1-mediated inhibition on the MAPK pathway significantly drives tumorigenesis and progression, enhances invasive and metastatic capacities, and is closely associated with therapeutic resistance. This article systematically reviews the structure and biological functions of SPRED1, its mutation profiles across different melanoma subtypes, and its regulatory mechanisms on the MAPK pathway. Furthermore, it discusses the associations of SPRED1 alteration with tumor malignant progression, as well as resistance to targeted therapy and immunotherapy. This review aims to provide a comprehensive theoretical basis for the precise diagnosis, treatment, and fundamental research of melanoma.