Epithelial mesenchymal transition and resistance in endocrine-related cancers

Biochim Biophys Acta Mol Cell Res. 2019 Sep;1866(9):1368-1375. doi: 10.1016/j.bbamcr.2019.05.003. Epub 2019 May 18.

Abstract

Epithelial to mesencyhmal transition (EMT) has a central role in tumor metastasis and progression. EMT is regulated by several growth factors and pro-inflammatory cytokines. The most important role in this regulation could be attributed to transforming growth factor-β (TGF-β). In breast cancer, TGF-β effect on EMT could be potentiated by Fos-related antigen, oncogene HER2, epidermal growth factor, or mitogen-activated protein kinase kinase 5 - extracellular-regulated kinase signaling. Several microRNAs in breast cancer have a considerable role either in potentiation or in suppression of EMT thus acting as oncogenic or tumor suppressive modulators. At present, possibilities to target EMT are discussed but the results of clinical translation are still limited. In prostate cancer, many cellular events are regulated by androgenic hormones. Different experimental results on androgenic stimulation or inhibition of EMT have been reported in the literature. Thus, a possibility that androgen ablation therapy leads to EMT thus facilitating tumor progression has to be discussed. Novel therapy agents, such as the anti-diabetic drug metformin or selective estrogen receptor modulator ormeloxifene were used in pre-clinical studies to inhibit EMT in prostate cancer. Taken together, the results of pre-clinical and clinical studies in breast cancer may be helpful in the process of drug development and identify potential risk during the early stage of that process.

Keywords: Breast cancer; Cadherin; Cell plasticity; Prostate cancer; miRNA.

Publication types

  • Review

MeSH terms

  • Benzopyrans / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Cadherins / metabolism
  • Cadherins / pharmacology
  • Cell Plasticity / drug effects
  • Cytokines
  • Disease Progression
  • Epidermal Growth Factor
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Inflammation
  • MAP Kinase Kinase 5
  • Male
  • Metformin / pharmacology
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-fos
  • Receptor, ErbB-2
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology

Substances

  • Benzopyrans
  • Cadherins
  • Cytokines
  • MicroRNAs
  • Proto-Oncogene Proteins c-fos
  • Transforming Growth Factor beta
  • ormeloxifene
  • Epidermal Growth Factor
  • Metformin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • MAP Kinase Kinase 5
  • MAP2K5 protein, human