Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells

Yu Pan, Xiuli Wang, Yanzhi Zhang, Juanjuan Qiao, Hironobu Sasano, Keely McNamara, Baoshan Zhao, Dongmei Zhang, Yuhua Fan, Lili Liu, Xueling Jia, Ming Liu, Sihang Song, Lin Wang

Research output: Contribution to journalArticle

Abstract

Proline-, glutamic acid–, leucine-rich protein 1 (PELP1) is a novel estrogen receptor (ER) coregulator, demonstrated distinctive characters from other ERα coregulators, and has been suggested to be involved in metastasis of several cancers. In ERα-positive breast cancer, PELP1 overexpression enhanced ruffles and filopodium-like structure stimulated by estradiol (E2) through extranuclear cell signaling transduction hereby increased cell motility. However, whether PELP1 is also involved in extracellular matrix remodeling of ERα-positive breast cancer cells is still unknown. In this study, we investigated the role of PELP1 in E2-induced MMP-9 expression and the underlined mechanism. The results demonstrated the following: E2-induced ERα-positive MCF-7 breast cancer cell MMP-9 mRNA and protein expression in a rapid response and concentration-dependent manner. Knocked down PELP1 significantly suppressed E2-induced MMP-9 expression. E2-bovine serum albumin (BSA), a large molecular membrane-impenetrable conjugate of E2, can also upregulate MMP-9 protein expression in MCF-7, and the action of E2-BSA can be abolished by PI3K inhibitor LY294002; treating MCF-7 simultaneously with PELP1-shRNA and LY294002 did not show synergetic inhibitory effect on E2-BSA-induced MMP-9 expression. Our results indicated that estrogen-induced MMP-9 expression in ER-positive breast cancer cells may be through PELP1-mediated PI3K/Akt signaling pathway.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalHormones and Cancer
Volume11
Issue number2
DOIs
Publication statusPublished - 2020 Apr 1

Keywords

  • Breast cancer
  • Estrogen
  • Matrix metalloproteinase-9
  • Proline-, glutamic acid–, leucine-rich protein 1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

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  • Cite this

    Pan, Y., Wang, X., Zhang, Y., Qiao, J., Sasano, H., McNamara, K., Zhao, B., Zhang, D., Fan, Y., Liu, L., Jia, X., Liu, M., Song, S., & Wang, L. (2020). Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells. Hormones and Cancer, 11(2), 87-96. https://doi.org/10.1007/s12672-020-00380-8