FABP4-mediated ERK phosphorylation promotes renal cancer cell migration

Evelina La Civita1, Rosa Sirica1, Felice Crocetto2

  • 1Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.

BMC Cancer
|March 30, 2025
PubMed

Insights

Fatty acid-binding protein 4 (FABP4) shows elevated levels in clear cell renal cell carcinoma (ccRCC) patients, promoting cancer cell migration and motility. FABP4 is a potential noninvasive biomarker and therapeutic target for ccRCC.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common and lethal kidney cancer subtype.
  • Fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2, is investigated for its role in ccRCC progression.

Purpose of the Study:

  • To investigate the potential role of FABP4 in ccRCC progression.
  • To evaluate FABP4 as a noninvasive biomarker and therapeutic target for ccRCC.

Main Methods:

  • Serum FABP4 levels were measured in ccRCC patients and healthy donors (HD).
  • In vitro studies using 786-O and ACHN cell lines analyzed proliferation and migration with recombinant FABP4 and adipocyte-conditioned media (Ad-CM).
  • Effects of FABP4 inhibitor BMS309403 and ERK phosphorylation were assessed.

Main Results:

  • Higher serum FABP4 levels were observed in ccRCC patients compared to HD.
  • FABP4 significantly increased cancer cell migration but not proliferation.
  • Ad-CM from ccRCC patients enhanced cell proliferation (in ACHN) and motility (in both cell lines), effects partially reversed by BMS309403.
  • FABP4-associated effects involved increased ERK phosphorylation.

Conclusions:

  • FABP4 plays a significant role in ccRCC progression, particularly in enhancing cell motility.
  • FABP4 is a potential noninvasive biomarker for ccRCC diagnosis.
  • FABP4 inhibition presents a potential therapeutic strategy for ccRCC.

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