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SIAH1/CTR9 axis promotes the epithelial-mesenchymal transition of hepatocellular carcinoma

Zhiyi Liu1,2,3, Pengchao Luo1,2,3, Kuan Cao1,2,3

  • 1Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Carcinogenesis
|April 11, 2023
PubMed

Insights

The study reveals that SIAH1 inhibits hepatocellular carcinoma (HCC) cell migration and invasion by regulating epithelial-mesenchymal transition (EMT). SIAH1 targets CTR9 for degradation, impacting EMT and offering a potential therapeutic strategy for HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • SIAH1 is implicated in various human cancers, including hepatocellular carcinoma (HCC).
  • The role of SIAH1 in regulating epithelial-mesenchymal transition (EMT) in HCC remains largely unexplored.
  • EMT is a critical process involved in cancer cell migration and invasion.

Purpose of the Study:

  • To investigate the effect of SIAH1 on EMT in HCC cells.
  • To identify interacting partners of SIAH1 in HCC.
  • To elucidate the molecular mechanism by which SIAH1 influences HCC progression.

Main Methods:

  • Yeast two-hybrid screening to identify SIAH1 interacting proteins.
  • Co-immunoprecipitation assays to validate protein interactions.
  • Analysis of ubiquitination and proteasomal degradation pathways.
  • Western blotting to assess protein levels in HCC tissues.

Main Results:

  • SIAH1 inhibits HCC cell migration and invasion by regulating EMT.
  • CTR9 (Cln Three Requiring 9) was identified as a direct interacting protein of SIAH1.
  • SIAH1 promotes EMT by negatively regulating CTR9 through K48-linked polyubiquitination and proteasomal degradation.
  • CTR9 protein levels are inversely correlated with SIAH1 levels in human HCC tissues.

Conclusions:

  • The SIAH1/CTR9 axis plays a crucial role in promoting EMT in HCC cells.
  • Targeting the SIAH1/CTR9 interaction presents a potential therapeutic strategy for HCC.
  • Understanding this axis provides insights into HCC progression and metastasis.

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