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Identification and characterization of a metastatic suppressor BRMS1L as a target gene of p53

Ryota Koyama1, Miyuki Tamura1, Takafumi Nakagaki1

  • 1Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.

Cancer Science
|October 15, 2017
PubMed

Insights

The p53 family activates breast cancer metastasis suppressor 1-like (BRMS1L), inhibiting cancer cell invasion and migration. Reduced BRMS1L expression correlates with poor prognosis in breast and brain cancers, suggesting it as a therapeutic target.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • The p53 family of tumor suppressors (p53, p63, p73) are critical transcription factors regulating cell fate.
  • These proteins control genes involved in cell cycle arrest, apoptosis, senescence, and genomic stability.
  • Emerging evidence highlights their role in regulating cancer cell invasion and migration.

Purpose of the Study:

  • To investigate the role of breast cancer metastasis suppressor 1-like (BRMS1L) in cancer metastasis.
  • To determine if BRMS1L is a downstream target of the p53 family.
  • To evaluate BRMS1L as a potential therapeutic target for cancer.

Main Methods:

  • Microarray analysis to identify genes upregulated by p53 family proteins.
  • Identification and characterization of p53 family response elements in the BRMS1L gene.
  • Functional assays including ectopic expression and siRNA knockdown of BRMS1L.
  • Analysis of clinical databases correlating BRMS1L expression with patient prognosis.

Main Results:

  • BRMS1L was found to be upregulated by p53, TAp63γ, and TAp73β.
  • Conserved p53 family binding sites were identified in the BRMS1L gene.
  • Ectopic BRMS1L expression inhibited cancer cell invasion and migration, while knockdown promoted these processes.
  • Reduced BRMS1L expression significantly correlated with poor prognosis in breast and brain cancer patients.

Conclusions:

  • BRMS1L acts as a mediator downstream of the p53 pathway.
  • BRMS1L functions as a suppressor of cancer cell invasion and migration, key steps in metastasis.
  • BRMS1L represents a potential therapeutic target for inhibiting cancer metastasis.
Keywords:
BRMS1Lcell invasioncell migrationp53p53 family

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