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Molecular Components of the RCC Grade

Tatsuto Ishimaru1

  • 1Division of Nephrology, Department of Internal Medicine, University of California, Davis, CA.

Seminars in Nephrology
|March 5, 2020
PubMed

Insights

Clear cell renal cell carcinoma (ccRCC) shows proteometabolomic reprogramming. Protein moonlighting and biomarker localization offer new therapeutic targets for this challenging kidney cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) remains difficult to treat with chemotherapy.
  • Recent proteomic and metabolomic studies reveal a grade-defined reprogramming model in ccRCC.
  • This model identifies potential therapeutic targets, many regulated by the MYC transcription factor.

Purpose of the Study:

  • To explore novel therapeutic strategies for ccRCC.
  • To investigate the role of protein moonlighting in ccRCC.
  • To understand the significance of subcellular localization of biomarkers in ccRCC progression.

Main Methods:

  • Proteomic and metabolomic analyses in a grade-defined manner.
  • Characterization of transcription factor control, including MYC.
  • Application of immunohistochemistry to study protein moonlighting and biomarker localization.

Main Results:

  • A global proteometabolomic reprogramming model for ccRCC was established.
  • MYC proto-oncogene, bHLH transcription factor, was identified as a key regulator.
  • Protein moonlighting was recognized as a factor in ccRCC metabolic reprogramming.
  • Subcellular localization of biomarkers emerged as a critical molecular signature.

Conclusions:

  • The proteometabolomic reprogramming model provides new drug targets for ccRCC.
  • Protein moonlighting and biomarker subcellular localization represent novel aspects of ccRCC pathology.
  • Further research into the functional significance of these findings is warranted for ccRCC treatment.
Keywords:
Fuhrman nuclear grade-defining biomarkersMycmetabolo-proteomicsprotein moonlighting

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