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The embryonic transcription factor Brachyury confers chordoma chemoresistance via upregulating CA9

Jiao Jian1, Nanzhe Zhong1, Dongjie Jiang1

  • 1Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical UniversityShanghai, China.

American Journal of Translational Research
|April 12, 2018
PubMed

Insights

Chordoma recurrence is linked to the embryonic transcription factor Brachyury, which promotes Paclitaxel resistance. Carbonic anhydrase IX (CA9) is identified as a key target gene involved in this resistance, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chordoma is a rare, locally invasive bone cancer of the axial skeleton with high recurrence rates.
  • Mechanisms underlying chordoma recurrence and resistance to therapies like chemotherapy and radiation are not fully understood.

Purpose of the Study:

  • To investigate the role of the embryonic transcription factor Brachyury in chordoma recurrence and chemoresistance.
  • To identify specific target genes regulated by Brachyury that contribute to treatment resistance.

Main Methods:

  • Establishment and characterization of primary chordoma cell lines (PCH1, PCH2).
  • Utilizing microarray analysis to identify genes regulated by Brachyury.
  • Chromatin immunoprecipitation assays to confirm gene targets.
  • Immunohistochemical staining to assess protein expression in chordoma tissues.

Main Results:

  • The embryonic transcription factor Brachyury was found to inhibit Paclitaxel-induced apoptosis in chordoma cells.
  • Carbonic anhydrase IX (CA9) was identified as a direct target gene of Brachyury.
  • CA9 expression positively correlated with Brachyury expression in chordoma tissues.
  • CA9 was demonstrated to be responsible for Paclitaxel resistance in chordoma cells.

Conclusions:

  • Brachyury plays a significant role in mediating Paclitaxel resistance in chordoma.
  • Carbonic anhydrase IX (CA9) is a key downstream effector of Brachyury in conferring chemoresistance.
  • CA9 represents a potential therapeutic target for overcoming Paclitaxel resistance in chordoma treatment.
Keywords:
BrachyuryChordomacarbonic anhydrase IXchemoresistance

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