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Updated: Aug 20, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Tat-hspb1 Suppresses Clear Cell Renal Cell Carcinoma (ccRCC) Growth via Lysosomal Membrane Permeabilization

Lin Zhang1, Guang-Zhi Jin2, Dong Li1

  • 1Departments of Urology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.

Cancers
|November 26, 2022
PubMed

Insights

A novel peptide, Tat-hspb1, derived from HSPB1, shows promise in treating clear cell renal cell carcinoma (ccRCC). It selectively targets and inhibits ccRCC cells while sparing normal cells, offering a potential new anticancer drug candidate.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer with increasing incidence and high mortality.
  • Bioactive peptides represent a significant class of natural medicines with therapeutic potential.

Purpose of the Study:

  • To explore the peptide profile of ccRCC using mass spectrometry-based peptidomic analysis.
  • To identify and develop novel peptide-based therapeutic agents for ccRCC.

Main Methods:

  • Peptidomic analysis of ccRCC and adjacent normal tissues.
  • Bioinformatic analysis to identify differentially expressed peptides.
  • Synthesis and characterization of a novel peptide, Tat-hspb1, by fusing an HSPB1-derived peptide to HIV-Tat.
  • In vitro assessment of Tat-hspb1's effects on ccRCC cell viability, apoptosis, proliferation, migration, and lysosomal localization.

Main Results:

  • 18,031 peptides were identified, with 105 unique peptides showing differential expression in ccRCC tissues.
  • Tat-hspb1 significantly inhibited ccRCC cell viability, proliferation, and migration.
  • Tat-hspb1 demonstrated lower cytotoxicity to normal epithelial cells compared to ccRCC cells.
  • Tat-hspb1 induced apoptosis in ccRCC cells, localized to lysosomes, and triggered lysosomal membrane permeabilization (LMP) and cathepsin D release.

Conclusions:

  • Tat-hspb1 is a promising peptide candidate for ccRCC therapy.
  • Tat-hspb1 exhibits selective anticancer activity through lysosomal-mediated apoptosis.
  • Further investigation into Tat-hspb1 as a novel anticancer drug is warranted.
Keywords:
apoptosislysosomal membrane permeabilization (LMP)peptiderenal cancer

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