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Prox1 Suppresses the Proliferation of Breast Cancer Cells via Direct Inhibition of c-Myc Gene Expression

Artemis Michail1,2, Dimitrios Gkikas1, Dimitris Stellas3

  • 1Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou Str., 115 27 Athens, Greece.

Cells
|July 29, 2023
PubMed

Insights

Prox1 suppresses breast cancer growth and metabolism by inhibiting c-Myc. Higher Prox1 levels in patients correlate with better breast cancer prognosis, indicating its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer remains a leading cause of cancer-related deaths in women globally.
  • Despite therapeutic advancements, understanding molecular mechanisms driving malignant progression is crucial for novel treatments.

Purpose of the Study:

  • To investigate the role of Prox1 as a potential regulator in breast cancer development and progression.
  • To explore Prox1's impact on cancer cell proliferation, metabolism, and tumor growth.

Main Methods:

  • Analysis of Prox1 expression in human breast tumors and correlation with patient prognosis.
  • In vitro experiments assessing Prox1's effects on breast cancer cell proliferation, migration, and the Warburg effect.
  • In vivo studies using xenograft mouse models to evaluate Prox1's anti-tumorigenic potential.
  • Investigation of Prox1's regulatory mechanism involving c-Myc transcription.

Main Results:

  • Reduced Prox1 expression was observed in human breast tumors; high Prox1 levels correlated with favorable patient prognosis.
  • Prox1 overexpression suppressed breast cancer cell proliferation, migration, and the Warburg effect without inducing apoptosis.
  • In vivo, Prox1 overexpression inhibited tumor growth in both heterotopic and orthotopic mouse models.
  • Prox1's anti-tumorigenic effects were mediated by direct repression of c-Myc transcription and its downstream targets.

Conclusions:

  • Prox1 acts as a tumor suppressor in breast cancer.
  • Prox1 exerts its anti-tumorigenic effects through the direct transcriptional repression of c-Myc.
  • Prox1 represents a promising therapeutic target for breast cancer treatment.
Keywords:
MPC1PDK1Warburg effectgene regulationmetabolism

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