Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway

Seung-Hyun Shin1,2,3, Ga Young Lee1,2,3, Mingyu Lee1,2,3

  • 1Department of Biomedical Science, BK21-plus Education Program, Seoul National University College of Medicine, Seoul, Korea.

Nature Communications
|October 7, 2018
PubMed

Insights

CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) promotes prostate cancer metastasis by activating nucleolin. Targeting CITED2 may offer a new strategy to prevent cancer spread.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Prostate cancer metastasis remains a significant challenge despite advancements in therapy.
  • Understanding the molecular mechanisms driving metastasis is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in prostate cancer metastasis.
  • To elucidate the molecular pathway through which CITED2 influences cancer progression.

Main Methods:

  • Analysis of CITED2 expression in metastatic prostate cancer tissues.
  • Investigating the interaction of CITED2 with PRMT5, p300, and nucleolin.
  • Evaluating the effect of the CITED2-nucleolin axis on cell migration and epithelial-mesenchymal transition (EMT).
  • Assessment of CITED2's role in a xenograft mouse model of prostate cancer metastasis.

Main Results:

  • CITED2 is highly expressed in metastatic prostate cancer and correlates with poor survival.
  • CITED2 activates nucleolin by acting as a molecular chaperone for PRMT5 and p300.
  • The CITED2-nucleolin axis promotes prostate cancer cell migration via EMT.
  • CITED2 enhances cancer metastasis in a preclinical mouse model.

Conclusions:

  • CITED2 plays a critical role in promoting prostate cancer metastasis.
  • The CITED2-nucleolin pathway is a key driver of cancer progression and spread.
  • CITED2 represents a potential therapeutic target for inhibiting prostate cancer metastasis.

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