Role of tumor necrosis factor alpha-induced protein 1 in paclitaxel resistance

Y Zhu1, Z Yao1, Z Wu2

  • 1Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui, China.

Oncogene
|August 6, 2013
PubMed

Insights

Increased tumor necrosis factor alpha-induced protein 1 (TNFAIP1) expression causes acquired resistance to paclitaxel by interfering with tubulin polymerization. TNFAIP1 represents a potential therapeutic target for overcoming paclitaxel resistance in epithelial cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Paclitaxel is a key chemotherapy agent for epithelial cancers.
  • Acquired resistance significantly limits paclitaxel's long-term efficacy.
  • Understanding resistance mechanisms is crucial for developing improved cancer therapies.

Purpose of the Study:

  • To identify novel genes associated with acquired paclitaxel resistance.
  • To elucidate the functional role of TNFAIP1 in paclitaxel resistance.
  • To explore TNFAIP1 as a potential therapeutic target.

Main Methods:

  • Investigated TNFAIP1 expression in paclitaxel-resistant cancer models.
  • Examined the interaction between TNFAIP1 and β-tubulin.
  • Assessed the impact of TNFAIP1 modulation on paclitaxel sensitivity in vitro and in vivo.
  • Analyzed TNFAIP1 regulation by Sp1.

Main Results:

  • Increased TNFAIP1 expression confers acquired resistance to paclitaxel.
  • TNFAIP1 competes with paclitaxel for β-tubulin binding, inhibiting polymerization and cell death.
  • Sp1 transcriptionally regulates TNFAIP1 expression.
  • In vivo studies showed TNFAIP1 overexpression reduces tumor response, while knockdown enhances it.

Conclusions:

  • TNFAIP1 is a novel gene conferring paclitaxel resistance.
  • TNFAIP1's mechanism involves direct interference with paclitaxel's action on tubulin.
  • Targeting TNFAIP1 may restore sensitivity to paclitaxel in resistant cancers.

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