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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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ACKR3 orchestrates Hedgehog signaling to promote renal cell carcinoma progression

Chao Tang1, Lin Li2, Qiang Xu1

  • 1National Clinical Research Center for Child Health of the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Molecular Carcinogenesis
|March 29, 2023
PubMed

Insights

Atypical chemokine receptor 3 (ACKR3) drives renal cell carcinoma (RCC) progression by orchestrating Hedgehog-GLI1 signaling. Targeting this pathway may offer novel therapeutic strategies for RCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • Renal cell carcinoma (RCC) is a significant urological malignancy with increasing mortality.
  • Understanding the molecular drivers of RCC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of atypical chemokine receptor 3 (ACKR3) in renal cell carcinoma (RCC) progression.
  • To elucidate the molecular mechanisms linking ACKR3 to the Hedgehog (Hh)-GLI1 signaling pathway in RCC.

Main Methods:

  • Analysis of ACKR3 expression in RCC tissues and its correlation with clinical outcomes.
  • Investigation of the interaction between ACKR3, Hh-GLI1 pathway components (GLI1, SMO), and CXCL12.
  • Assessment of the impact of the ACKR3-Hh-GLI1 axis on RCC progression.

Main Results:

  • ACKR3 expression is elevated in RCC tissues and correlates with poor clinical outcomes and higher GLI1 expression.
  • GLI1 directly binds to the ACKR3 gene, promoting its transcription.
  • The CXCL12-ACKR3 interaction enhances Hh pathway activation by upregulating SMO phosphorylation, driving RCC progression.

Conclusions:

  • ACKR3 plays a critical role in promoting RCC progression through the Hh-GLI1 signaling pathway.
  • The findings highlight the ACKR3-Hh-GLI1 axis as a potential therapeutic target for renal cell carcinoma.
  • Targeting ACKR3 or its associated signaling may offer a novel treatment strategy for RCC.
Keywords:
ACKR3CXCL12GLI1Hedgehogrenal cell carcinoma

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