Scholarlink

<p>S-palmitoylation, a reversible lipid-based post-translational modification, is notably elevated in colorectal cancer (CRC) due to common lipid metabolism disorders. It has been reported to play crucial roles in regulating membrane composition, cell proliferation, and metastasis in various malignancies such as pancreatic and breast cancers. However, its role in the progression of CRC remains poorly understood. ZDHHC9, a member of the palmitoyl transferase family, is significantly upregulated in CRC patients and correlates with poor prognosis. Knockdown of ZDHHC9 impairs CRC cell proliferation and migration both in vitro and in vivo. RNA sequencing revealed that ZDHHC9 depletion markedly downregulates the cAMP signaling pathway. Mechanistically, ZDHHC9 knockdown impairs ADCY4 activity by reducing S-palmitoylation of KLF5 at cysteine 438, thereby modulating the ZDHHC9/KLF5/ADCY4 axis and downstream cAMP/PKA/CREB signaling to influence CRC cell proliferation and migration. Our findings demonstrate that ZDHHC9 promotes CRC progression by regulating intracellular cAMP levels through KLF5 palmitoylation, providing a novel therapeutic perspective targeting palmitoylation in CRC.</p><p></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

ZDHHC9-mediated KLF5 palmitoylation enhances the cAMP/PKA/CREB axis to promote colorectal cancer progression

  • 期刊论文

  • 发表日期：

    2026年3月25日

查看全文
  • Hao Zhang,
  • Yuan Tian,
  • Zeyu Xiang,
  • Feng Han,
  • Miaomiao Chen,
  • Chunhui Jiang,
  • Ye Liu,
  • Hanbing Xue,
  • Lipeng Hu,
  • Chunjie Xu,
  • Lei Gu,
  • Qing Xu

摘要

S-palmitoylation, a reversible lipid-based post-translational modification, is notably elevated in colorectal cancer (CRC) due to common lipid metabolism disorders. It has been reported to play crucial roles in regulating membrane composition, cell proliferation, and metastasis in various malignancies such as pancreatic and breast cancers. However, its role in the progression of CRC remains poorly understood. ZDHHC9, a member of the palmitoyl transferase family, is significantly upregulated in CRC patients and correlates with poor prognosis. Knockdown of ZDHHC9 impairs CRC cell proliferation and migration both in vitro and in vivo. RNA sequencing revealed that ZDHHC9 depletion markedly downregulates the cAMP signaling pathway. Mechanistically, ZDHHC9 knockdown impairs ADCY4 activity by reducing S-palmitoylation of KLF5 at cysteine 438, thereby modulating the ZDHHC9/KLF5/ADCY4 axis and downstream cAMP/PKA/CREB signaling to influence CRC cell proliferation and migration. Our findings demonstrate that ZDHHC9 promotes CRC progression by regulating intracellular cAMP levels through KLF5 palmitoylation, providing a novel therapeutic perspective targeting palmitoylation in CRC.