Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF-κB-mediated IKKβ expression

Yi Hui Wu, Yu Fang Huang, Tzu Hao Chang, Cheng Yang Chou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression. TWIST1 messenger RNA levels positively associated with COL11A1 messenger RNA expression levels in ovarian tumors. High TWIST1 expression levels were significantly associated with a progression-free interval of ≤ 6 months (p = 0.001) and death (p = 0.040). In addition, patients with high TWIST1 mRNA levels had significantly shorter 5-year overall-survival (p = 0.004) and progression-free survival (p = 0.009) rates, compared to patients with low TWIST1 levels. Increased TWIST1 expression caused by COL11A1-induced transcription of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ) gene occurred via increased SP1 phosphorylation and binding to the IKKβ promoter. COL11A1-mediated nuclear factor-kappa B activation, via transcriptional activation of IKKβ, promoted TWIST1, Mcl-1, and GAS6 expression, which were associated with chemoresistance and anti-apoptosis in ovarian cancer cells. We suggest that IKKβ and TWIST1 can potentially be targeted in patients with COL11A1-positive ovarian cancer.

Original languageEnglish
Pages (from-to)2305-2317
Number of pages13
JournalInternational Journal of Cancer
Volume141
Issue number11
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

Ovarian Neoplasms
Apoptosis
Messenger RNA
Twist-Related Protein 1
Collagen Type XI
I-kappa B Kinase
Basic Helix-Loop-Helix Transcription Factors
NF-kappa B
Small Interfering RNA
Transcriptional Activation
Disease-Free Survival
Down-Regulation
Phosphorylation
Survival
Genes
Neoplasms
Proteins
TP protocol

Keywords

  • anti-apoptosis
  • chemoresistance
  • collagen type XI alpha 1
  • epithelial ovarian carcinoma
  • TWIST1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF-κB-mediated IKKβ expression. / Wu, Yi Hui; Huang, Yu Fang; Chang, Tzu Hao; Chou, Cheng Yang.

In: International Journal of Cancer, Vol. 141, No. 11, 01.12.2017, p. 2305-2317.

Research output: Contribution to journalArticle

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