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  1. Home
  2. Afp-hsp90 Mediated Myc/met Activation Promotes Tumor Progression In Hepatocellular Carcinoma And Gastric Cancers.
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  2. Afp-hsp90 Mediated Myc/met Activation Promotes Tumor Progression In Hepatocellular Carcinoma And Gastric Cancers.

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AFP-HSP90 mediated MYC/MET activation promotes tumor progression in hepatocellular carcinoma and gastric cancers.

Ziqi Lin1,2,3, Rulu Pan1,3, Liyue Wu1,3

  • 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

Cancer Cell International
|August 12, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Alpha-fetoprotein (AFP) stabilizes oncoproteins c-MYC and c-MET by interacting with HSP90, promoting liver and gastric tumor growth. Inhibiting AFP or HSP90 may enhance cancer therapy effectiveness.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Alpha-fetoprotein (AFP) elevation is a biomarker for diseases, notably hepatocellular carcinoma (HCC).
  • Intracellular AFP's role in promoting tumorigenesis has been previously suggested.

Purpose of the Study:

  • To investigate the mechanism by which AFP promotes tumor progression.
  • To identify AFP's role in the stabilization of key oncoproteins.
  • To explore therapeutic strategies targeting the AFP-HSP90 interaction.

Main Methods:

  • Investigated the interaction between AFP, heat shock protein 90 (HSP90), and oncoproteins c-MYC and c-MET.
  • Assessed the effect of AFP on the ubiquitination and degradation of HSP90 client proteins.
  • Evaluated the cytotoxicity of chemotherapeutic agents in the presence of AFP or HSP90 inhibition.

Main Results:

  • Discovered that AFP enhances the stability of oncoproteins c-MYC and c-MET, facilitating liver and gastric tumor progression.
  • Identified AFP as a novel co-chaperone of HSP90, regulating the stabilization of its client proteins.
  • Demonstrated that inhibiting AFP or HSP90 increases the effectiveness of chemotherapy in AFP-producing cancer cells.

Conclusions:

  • AFP promotes tumor progression by stabilizing c-MYC and c-MET via interaction with HSP90.
  • The AFP-HSP90-mediated pathway offers a new therapeutic target for AFP-producing liver and gastric cancers.
  • Targeting AFP or HSP90 presents a promising strategy to enhance chemotherapeutic efficacy.