Wu Y-H et al.

Summary - It is known that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel. Based on the current study, IKKβ and TWIST1 can serve as potential targets in patients with COL11A1-positive ovarian cancer. 

Methods
Regulation of twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) by COL11A1 was elucidated.

Results
Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel by down-regulating TWIST1 expression. 
TWIST1 messenger RNA levels were positively associated with COL11A1 messenger RNA expression levels in ovarian tumors.
High TWIST1 expression levels were significantly associated with a progression-free interval less than or equal to 6 months and death.
High TWIST1 mRNA levels were associated with significantly shorter 5-year overall-survival and progression-free survival 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.