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PFKFB4 is overexpressed in clear-cell renal cell carcinoma promoting pentose phosphate pathway that mediates

Chenchen Feng1,2, Yuqing Li1,2, Kunping Li1,2

  • 1Department of Urology, Huashan Hospital, Fudan University, 12 Middle Urumqi Rd, 200040, Shanghai, PR China.

Journal of Experimental & Clinical Cancer Research : CR
|October 1, 2021
PubMed
Abstract

Insights

6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) is a novel kinase driving clear-cell renal cell carcinoma (ccRCC) progression. Targeting PFKFB4 may overcome Sunitinib resistance in ccRCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Kinases are crucial in clear-cell renal cell carcinoma (ccRCC) pathogenesis.
  • Identifying novel, druggable, and protumorigenic kinases is essential for ccRCC treatment.
  • This study focuses on a specific kinase involved in ccRCC progression.

Purpose of the Study:

  • To identify and characterize a novel kinase involved in ccRCC.
  • To investigate the role of this kinase in tumor growth, metastasis, and drug resistance.
  • To explore therapeutic strategies targeting this kinase in ccRCC.

Main Methods:

  • Differential gene expression analysis of public datasets and microarray validation.
  • Multi-omics analysis (metabolomics, phosphoproteomics) and in vitro/in vivo functional studies.
  • Investigation of kinase activity, downstream targets, and drug resistance mechanisms.

Main Results:

  • 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) was overexpressed in ccRCC tumors, correlating with advanced stage and poor prognosis.
  • PFKFB4 knockdown inhibited cancer cell proliferation, migration, and wound healing.
  • PFKFB4 regulates the pentose phosphate pathway (PPP) via NCOA3 phosphorylation and overcomes Sunitinib resistance.
  • PFKFB4 mRNA is transcribed by HIF1α despite 3p deletion.

Conclusions:

  • PFKFB4 is a key regulator of PPP activity in ccRCC, modulated by NCOA3 phosphorylation.
  • Targeting PFKFB4 shows potential for overcoming Sunitinib resistance in ccRCC.
  • PFKFB4 represents a promising therapeutic target for ccRCC treatment.
Keywords:
Clear-cell renal cell carcinomaPFKFB4Pentose phosphate pathwayResistanceSunitinib

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