Scholarlink

<p>Osteosarcoma is a highly heterogeneous and aggressive malignancy with a strong propensity for metastasis, highlighting the need to define its molecular drivers. Here, we report that ASB7 promotes tumor cell protrusion formation, invasion, migration, and lung metastasis. High expression of ASB7 is correlated with a poor prognosis. ASB7 forms an E3 ubiquitin ligase complex with CUL5 to ubiquitinate ATF2 at K383 and promote its proteasomal degradation. ATF2 reduction impairs HDAC6 recruitment to the ITGB2 promoter, thereby alleviating the transcriptional repression of ITGB2. Elevated ITGB2 expression subsequently promotes tumor lung metastasis. Our findings reveal that the ASB7-ATF2/HDAC6-ITGB2 axis regulates osteosarcoma metastasis and suggest potential treatment targets.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

ASB7 promotes osteosarcoma lung metastasis through ubiquitin-mediated degradation of ATF2

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月5日

查看全文
  • Yezi Zou,
  • Jianliang Zhong,
  • Lanqing Huo,
  • Jiali Chen,
  • Xinhao Yu,
  • Jingxuan Wang,
  • Zhenxuan Chen,
  • Lifeng Yin,
  • Cuiling Zeng,
  • Xia Zhang,
  • Shan Han,
  • Ruhua Zhang,
  • Xing-Ding Zhang,
  • Tiebang Kang,
  • Liwen Zhou

摘要

Osteosarcoma is a highly heterogeneous and aggressive malignancy with a strong propensity for metastasis, highlighting the need to define its molecular drivers. Here, we report that ASB7 promotes tumor cell protrusion formation, invasion, migration, and lung metastasis. High expression of ASB7 is correlated with a poor prognosis. ASB7 forms an E3 ubiquitin ligase complex with CUL5 to ubiquitinate ATF2 at K383 and promote its proteasomal degradation. ATF2 reduction impairs HDAC6 recruitment to the ITGB2 promoter, thereby alleviating the transcriptional repression of ITGB2. Elevated ITGB2 expression subsequently promotes tumor lung metastasis. Our findings reveal that the ASB7-ATF2/HDAC6-ITGB2 axis regulates osteosarcoma metastasis and suggest potential treatment targets.