TY - JOUR
T1 - Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells
AU - Pan, Yu
AU - Wang, Xiuli
AU - Zhang, Yanzhi
AU - Qiao, Juanjuan
AU - Sasano, Hironobu
AU - McNamara, Keely
AU - Zhao, Baoshan
AU - Zhang, Dongmei
AU - Fan, Yuhua
AU - Liu, Lili
AU - Jia, Xueling
AU - Liu, Ming
AU - Song, Sihang
AU - Wang, Lin
N1 - Funding Information:
This work was supported by the Fundamental Research Funds for the Provincial Universities (Grant No. JFXN201906 and JFXN201910), the Scientific Research Fund of Harbin Medical University-Daqing (Grant No. DQ2013-1), and the Postgraduate Tutor Foundation of Harbin Medical University-Daqing (Grant No. DSJJ2015003).
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Estrogen
KW - Matrix metalloproteinase-9
KW - Proline-, glutamic acid–, leucine-rich protein 1
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U2 - 10.1007/s12672-020-00380-8
DO - 10.1007/s12672-020-00380-8
M3 - Article
C2 - 32037484
AN - SCOPUS:85079179913
VL - 11
SP - 87
EP - 96
JO - Hormones and Cancer
JF - Hormones and Cancer
SN - 1868-8497
IS - 2
ER -
