Signaling pathways in leiomyoma: Understanding pathobiology and implications for therapy

Mostafa A. Borahay, Ayman Al Hendy, Gokhan Kilic, Darren Boehning

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying patho biology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-β)/Smad; wingless-type (Wnt)/β-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multi factorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics.

Original languageEnglish (US)
Pages (from-to)242-256
Number of pages15
JournalMolecular Medicine
Volume21
DOIs
StatePublished - 2015

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Leiomyoma
Vitamin D
Intercellular Signaling Peptides and Proteins
Medical Economics
Catenins
Neoplasms
Peroxisome Proliferator-Activated Receptors
Tretinoin
Mitogen-Activated Protein Kinases
Cytogenetics
Transforming Growth Factor beta
Smooth Muscle Myocytes
Estrogens
Therapeutics
Steroids

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Signaling pathways in leiomyoma : Understanding pathobiology and implications for therapy. / Borahay, Mostafa A.; Al Hendy, Ayman; Kilic, Gokhan; Boehning, Darren.

In: Molecular Medicine, Vol. 21, 2015, p. 242-256.

Research output: Contribution to journalArticle

Borahay, Mostafa A. ; Al Hendy, Ayman ; Kilic, Gokhan ; Boehning, Darren. / Signaling pathways in leiomyoma : Understanding pathobiology and implications for therapy. In: Molecular Medicine. 2015 ; Vol. 21. pp. 242-256.
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