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TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer

Song-Fa Zhang1, Xin-Yu Wang, Zhi-Qin Fu

  • 1a Women's Reproductive Health Laboratory of Zhejiang Province; Women's Hospital; School of Medicine ; Zhejiang University ; Hangzhou , China.

Autophagy
|January 22, 2015
PubMed

Insights

TXNDC17 protein is highly expressed in paclitaxel-resistant ovarian cancer, promoting drug resistance by inducing autophagy. Targeting TXNDC17 could be a new therapeutic strategy for ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Paclitaxel is a key chemotherapy for ovarian cancer.
  • Drug resistance limits paclitaxel efficacy.
  • The mechanism of paclitaxel resistance in ovarian cancer is not fully understood.

Purpose of the Study:

  • To identify key molecules involved in paclitaxel resistance in ovarian cancer.
  • To elucidate the role of TXNDC17 in paclitaxel resistance.
  • To investigate the potential of TXNDC17 as a therapeutic target.

Main Methods:

  • Proteomic analysis (LC-MS/MS label-free quantitative proteomics) to screen differentially expressed proteins.
  • Quantitative real-time PCR and Western blotting to assess gene and protein expression.
  • Cell viability assays to evaluate paclitaxel resistance.
  • siRNA-mediated gene silencing and plasmid transfection to manipulate TXNDC17 and BECN1 expression.
  • Autophagy assays to measure autophagosome formation and autophagic flux.

Main Results:

  • TXNDC17 was identified as a protein highly expressed in paclitaxel-resistant ovarian cancer cells and tissues.
  • High TXNDC17 expression correlated with poorer prognostic factors and reduced survival in ovarian cancer patients.
  • Paclitaxel treatment induced TXNDC17 and BECN1 expression, enhancing autophagy and conferring chemoresistance.
  • TXNDC17 inhibition reduced autophagy and paclitaxel resistance, while its overexpression increased them.
  • BECN1 downregulation attenuated TXNDC17-induced autophagy and cytoprotection.

Conclusions:

  • TXNDC17 induces autophagy, mediated by BECN1, leading to paclitaxel resistance in ovarian cancer.
  • TXNDC17 represents a potential predictive biomarker and therapeutic target for ovarian cancer.
Keywords:
95% CI, 95% confidence intervalALDOC, aldolase C, fructose-bisphosphateATG5, autophagy-related 5BECN1BECN1, Beclin 1, autophagy-relatedBafA1, bafilomycin A1CNN3, calponin 3, acidicDAPI, 4', 6-diamidino-2-phenylindoleFLNA, filamin A, αGO, gene ontologyGenMAPP, gene microarray pathway profilerHBSS, Hank's balanced salt solutionHR, hazard ratioKEGG, Kyoto encyclopedia of genes and genomeLC-MS/MS, liquid chromatography-mass spectrometry/ mass spectrometryMAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 βOS, overall survivalPFS, progression-free survivalPGAM1, phosphoglycerate mutase 1 (brain)SQSTM1, sequestosome 1TNF, tumor necrosis factorTXN, thioredoxinTXNDC17TXNDC17, thioredoxin domain containing 17UTP23, small subunit (SSU) processome component, homolog (yeast)autophagyovarian cancerpaclitaxel resistancesiRNA, short interfering RNA

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