Molecular Medicine

, Volume 21, Issue 1, pp 242–256 | Cite as

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

  • Mostafa A. Borahay
  • Ayman Al-Hendy
  • Gokhan S. Kilic
  • Darren Boehning
Review Article


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 pathobiology. 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 multifactorial 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.



This work was supported, in whole or in part, by the following grants to Mostafa Borahay: NIH K12 Career Development Award 5K12HD001269-12 and an award from the Institute for Translational Sciences at the University of Texas Medical Branch supported in part by NCATS, NIH Grant CTSA UL1TR000071. This work also was supported by the following grants to Darren Boehning: NIH Grants 1R01GM081685-01 and 3R01GM081685-03S1 and startup funds provided by the University of Texas Health Science Center at Houston.


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Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyUniversity of Texas Medical BranchGalvestonUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Texas Health Science CenterHoustonUSA
  3. 3.Department of Obstetrics and Gynecology, Medical College of GeorgiaGeorgia Regents UniversityAugustaUSA

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