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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated

Qi Wang1,2, Su Gao3,4, Yi Shou1,2

  • 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

International Journal of Biological Sciences
|March 16, 2023
PubMed

Insights

Absent in melanoma 2 (AIM2) promotes renal cell carcinoma (RCC) progression and sunitinib resistance by inhibiting ferroptosis via the FOXO3a-ACSL4 pathway. This discovery offers new therapeutic targets for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Renal cell carcinoma (RCC) is aggressive, with patients often developing resistance to targeted therapies.
  • The absent in melanoma 2 (AIM2) protein's role in disease is under investigation.
  • Identifying novel biomarkers and therapeutic targets for RCC is crucial.

Purpose of the Study:

  • To investigate the role of AIM2 in renal cell carcinoma (RCC) progression.
  • To explore AIM2's involvement in resistance to sunitinib, a targeted therapy for RCC.
  • To elucidate the molecular mechanisms underlying AIM2's function in RCC.

Main Methods:

  • Identification of AIM2 as a potential biomarker in RCC.
  • Experimental models to study AIM2's effect on RCC progression and drug resistance.
  • Analysis of the inflammasome pathway's involvement.
  • Investigation of AIM2's interaction with FOXO3a, ACSL4, and ferroptosis.

Main Results:

  • AIM2 was identified as a novel biomarker promoting RCC progression.
  • AIM2 conferred resistance to sunitinib in an inflammasome-independent manner.
  • AIM2 induced FOXO3a phosphorylation and proteasome degradation.
  • This process inhibited ACSL4 expression, leading to reduced ferroptosis.

Conclusions:

  • AIM2 promotes RCC progression and sunitinib resistance through the FOXO3a-ACSL4 axis-regulated ferroptosis pathway.
  • AIM2 represents a potential therapeutic target for improving RCC treatment outcomes.
  • Understanding this mechanism provides new insights for RCC diagnosis and therapy.
Keywords:
ACSL4Absent in melanoma2FerroptosisRenal cell carcinomaSunitinib resistance

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