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ERK/MAPK Signalling Pathway Regulates MMP2 through ETS1 in Renal Clear Cell Carcinoma

Hai-Bin Chen1,2, Wei Li1, Zhan Yang1

  • 1Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, 050061, China.

Current Molecular Medicine
|May 31, 2023
PubMed
Abstract

Insights

High ETS1 expression correlates with clear cell renal cell carcinoma (ccRCC) progression. Targeting ETS1 and ERK may inhibit ccRCC cell proliferation, migration, and invasion, suggesting ETS1 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • ETS1 expression is elevated in clear cell renal cell carcinoma (ccRCC) tissues.
  • The precise role of ETS1 in ccRCC pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the association between ETS1 expression and ccRCC progression.
  • To elucidate the functional role of ETS1 in ccRCC cell proliferation, migration, and invasion.

Main Methods:

  • Protein-protein interaction network analysis using STRING.
  • Cell viability, proliferation, migration, and invasion assays (CCK-8, clonogenic, wound-healing, Transwell).
  • Western blot analysis for protein expression; PERK and ERK pathway inhibitors were utilized.

Main Results:

  • Significantly increased ETS1 expression in ccRCC tissues and its correlation with advanced tumor stage, lymph node metastasis, and higher grades (p<0.05).
  • ETS1 knockdown and PERK inhibition suppressed ccRCC cell proliferation, migration, and invasion.
  • ETS1 knockdown reduced MMP-2 expression; ERK inhibition affected both ETS1 and MMP-2 expression.

Conclusions:

  • Elevated ETS1 expression is linked to ccRCC progression.
  • ETS1 promotes ccRCC proliferation via MMP2 upregulation.
  • Combined ETS1 knockdown and ERK inhibition show therapeutic potential for ccRCC.
Keywords:
ETS1MMP2Renal clear cell carcinomacell proliferationmigration.pERK

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