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CBX7 binds the E-box to inhibit TWIST-1 function and inhibit tumorigenicity and metastatic potential

Juanni Li1, Ayesha B Alvero2, Sudhakar Nuti2

  • 1Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.

Oncogene
|March 25, 2020
PubMed

Insights

Ovarian cancer deaths stem from widespread micrometastasis. A study reveals that suppressing CBX7 in secondary ovarian cancer cells (sEOC) reactivates TWIST-1, promoting metastasis and predicting patient prognosis.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Oncology

Background:

  • Ovarian cancer mortality is primarily linked to widespread micrometastasis.
  • The cellular phenotype and metastatic mechanisms of epithelial ovarian cancer cells (sEOC) at secondary sites remain incompletely understood.
  • Epithelial-mesenchymal transition is crucial for acquiring metastatic potential.

Purpose of the Study:

  • To investigate the molecular phenotype of secondary epithelial ovarian cancer cells (sEOC).
  • To elucidate the mechanisms governing the establishment of metastatic ovarian tumors.
  • To identify potential therapeutic targets and prognostic markers in ovarian cancer.

Main Methods:

  • Utilized in vitro and in vivo models of epithelial ovarian cancer.
  • Analyzed the expression and function of TWIST-1 and CBX7 in sEOC.
  • Investigated the impact of CBX7 deletion on TWIST-1 transcriptional activity and cellular phenotype.
  • Correlated CBX7 and TWIST-1 expression with clinical outcomes.

Main Results:

  • Secondary EOC cells (sEOC) exhibit an epithelial morphology but retain high TWIST-1 expression.
  • TWIST-1 is transcriptionally inactive in sEOC due to CBX7 binding.
  • CBX7 deletion in sEOC reactivates TWIST-1, induces mesenchymal transition, and enhances tumorigenicity.
  • A novel subclassification based on CBX7 and TWIST-1 expression predicts ovarian cancer patient prognosis.

Conclusions:

  • CBX7 regulates TWIST-1 activity in sEOC, enabling a reversible epithelial-mesenchymal phenotype.
  • This regulatory mechanism contributes to ovarian cancer metastasis and secondary tumor formation.
  • CBX7 and TWIST-1 expression serve as valuable biomarkers for predicting ovarian cancer outcomes.

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