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Tat-HSPE1 suppresses clear cell renal cell carcinoma growth through lysosome-dependent cell death

Lin Zhang1, Weiyuan Li1,2, Min Liu3

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

Frontiers in Pharmacology
|May 18, 2026
PubMed

Insights

A novel peptide, Tat-HSPE1, derived from Heat Shock Protein Family E Member 1 (HSPE1), shows promise for treating clear cell renal cell carcinoma (ccRCC). It selectively kills ccRCC cells by inducing DNA damage and activating autophagy, while suppressing tumor growth in vivo.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype.
  • Current first-line treatments have limited efficacy in advanced ccRCC.
  • Bioactive peptides are emerging as potential anticancer therapeutics.

Purpose of the Study:

  • To identify and characterize novel peptide therapeutics for ccRCC.
  • To investigate the therapeutic potential of a fusion peptide derived from Heat Shock Protein Family E Member 1 (HSPE1), designated Tat-HSPE1.
  • To elucidate the molecular mechanisms underlying Tat-HSPE1's anticancer activity.

Main Methods:

  • Peptidomics analysis of ccRCC tissues and adjacent normal tissues.
  • In vitro cell death assays on ccRCC and normal cells.
  • Mechanism of action studies including DNA damage, apoptosis, and lysosomal membrane permeabilization assays.
  • Confocal microscopy to track peptide localization and protein interactions.
  • In vivo xenograft tumor growth suppression studies.

Main Results:

  • A novel peptide derived from HSPE1 was identified.
  • Engineered Tat-HSPE1 selectively induced cell death in ccRCC cells with minimal toxicity to normal cells.
  • Tat-HSPE1 induced DNA damage, caspase-independent apoptosis, and lysosomal membrane permeabilization.
  • Tat-HSPE1 accumulated in the nucleolus, interacted with CTTNBP2NL, and promoted autophagy.
  • Tat-HSPE1 significantly suppressed ccRCC xenograft tumor growth in vivo.

Conclusions:

  • Tat-HSPE1 demonstrates selective cytotoxicity against ccRCC cells.
  • Tat-HSPE1 exerts its effects through DNA damage, apoptosis, and autophagy modulation.
  • Tat-HSPE1 shows significant therapeutic potential for ccRCC treatment.
Keywords:
CTTNBP2NLautophagyheat shock proteinslysosomal membrane permeabilization (lmp)peptiderenal cancer

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