Integrin αvβ3 in the mediating effects of dihydrotestosterone and resveratrol on breast cancer cell proliferation

Yih Ho, Li Zi-Lin, Shih Ya-Jung, Chen Yi-Ru, Kuan Wang, Jacqueline Whang-Peng, Lin Hung-Yun, Paul J. Davis

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Hormones and their receptors play an important role in the development and progression of breast cancer. Hormones regulate the proliferation of breast cancer cells through binding between estrogen or progestins and steroid receptors that may reside in the cytoplasm or be transcriptionally activated as steroid–protein nuclear receptor complexes. However, receptors for nonpeptide hormones also exist in the plasma membrane. Via those receptors, hormones are able to stimulate breast cancer cell proliferation when activated. Integrins are heterodimeric structural proteins of the plasma membrane. Their primary functions are to interact with extracellular matrix proteins and growth factors. Recently, integrin αvβ3 has been identified as a receptor for nonpeptide hormones, such as thyroid hormone and dihydrotestosterone (DHT). DHT promotes the proliferation of human breast cancer cells through binding to integrin αvβ3. A receptor for resveratrol, a polyphenol stilbene, also exists on this integrin in breast cancer cells, mediating the anti-proliferative, pro-apoptotic action of the compound in these cells. Unrelated activities of DHT and resveratrol that originate at integrin depend upon downstream stimulation of mitogen-activated protein kinase (MAPK, ERK1/2) activity, suggesting the existence of distinct, function-specific pools of ERK1/2 within the cell. This review will discuss the features of these receptors in breast cancer cells, in turn suggesting clinical applications that are based on the interactions of resveratrol/DHT with integrin αvβ3 and other androgen receptors.
Original languageEnglish
Article number2906
JournalInternational Journal of Molecular Sciences
Volume21
Issue number8
DOIs
Publication statusPublished - Apr 21 2020

Keywords

  • Breast cancer
  • Dihydrotestosterone
  • Integrin αvβ3
  • Resveratrol

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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