Decrease of phosphorylated proto-oncogene CREB at Ser 133 site inhibits growth and metastatic activity of renal cell

Xue Wang1, Yu Ren, Haihui Zhuang

  • 1Ningbo University, School of Medicine , Ningbo 315211 , China.

Abstract

Insights

Phosphorylated CREB (pCREB) at Ser 133 drives renal cell carcinoma (RCC) growth and metastasis. Inhibiting pCREB significantly reduces tumor progression and spread, offering a potential therapeutic target for kidney cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cyclic-AMP-responsive element-binding protein (CREB) is a proto-oncogenic transcription factor implicated in tumor progression.
  • Previous studies indicated that blocking the CREB binding site at Ser 133 inhibits target gene expression relevant to cancer.
  • The role of phosphorylated CREB (pCREB) at Ser 133 in renal cell carcinoma (RCC) warrants further investigation.

Purpose of the Study:

  • To investigate the role of phosphorylated CREB (pCREB) at Ser 133 in the growth and metastasis of renal cell carcinoma (RCC).
  • To determine if targeting pCREB at Ser 133 can inhibit RCC progression.

Main Methods:

  • Utilized immunohistochemistry, xenograft models in nude mice, and cell-based assays (proliferation, invasion, migration).
  • Employed fluorescent immunocytochemistry and Western analysis in an immortalized proximal tubule epithelial cell line and clear-cell RCC.
  • Bioinformatic analysis was performed to investigate potential molecular mechanisms.

Main Results:

  • Knockdown of pCREB significantly inhibited RCC cell growth in vivo.
  • Suppression of pCREB levels reduced cell migration and invasion in vitro, correlating with decreased expression of MMP-2, MMP-9, and EMT-related proteins.
  • Vimentin expression and localization remained unchanged, potentially due to the absence of a CRE sequence in its promoter.

Conclusions:

  • Decreasing the level of pCREB at Ser 133 effectively inhibits the growth and metastasis of renal cell carcinoma (RCC).
  • Targeting the Ser 133 site of pCREB presents a potential therapeutic strategy for managing RCC.

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