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Estrogen receptor signaling mediates leptin-induced growth of breast cancer cells via autophagy induction

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Author(s)
Pawan Kumar RautDong Young ChoiSang Hyun KimJin Tae HongTaeg Kyu KwonJee Heon JeongPil-Hoon Park
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Oncotarget
Issued Date
2017
Volume
8
Issue
65
Keyword
apoptosisautophagybreast cancerestrogen receptorleptin
Abstract
Leptin, a hormone derived from adipose tissue, promotes growth of cancer cells via multiple mechanisms. Estrogen receptor signaling is also known to stimulate the growth of breast cancer cells. However, the involvement of estrogen receptor signaling in the oncogenic actions of leptin and its underlying mechanisms are not clearly understood. Herein, we investigated mechanisms for estrogen receptor signaling-mediated growth of breast cancer cells, particularly focusing on autophagy, which plays a crucial role in leptin-induced tumor growth. Inhibition of estrogen receptor signaling via gene silencing or treatment with a pharmacological inhibitor (tamoxifen) abolished leptin-induced growth of MCF-7 human breast cancer cells. Interestingly, leptin-induced autophagy activation, determined by up-regulation of autophagy-related genes and autophagosome formation, was also significantly suppressed by inhibiting estrogen receptor signaling. Moreover, inhibition of estrogen receptor markedly prevented leptin-induced activation of AMPK/FoxO3A axis, which plays a crucial role in autophagy induction. Leptin-induced cell cycle progression and Bax down-regulation were also prevented by treatment with tamoxifen. The pivotal roles of estrogen receptor signaling in leptin-induced cell cycle progression, apoptosis suppression, and autophagy induction were further confirmed in MCF-7 tumor xenograft model. Taken together, these results demonstrate that estrogen receptor signaling plays a key role in leptin-induced growth of breast cancer cells via autophagy activation.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Pawan Kumar Raut et al. (2017). Estrogen receptor signaling mediates leptin-induced growth of breast cancer cells via autophagy induction. Oncotarget, 8(65), 109417–109435. doi: 10.18632/oncotarget.22684
Type
Article
ISSN
1949-2553
DOI
10.18632/oncotarget.22684
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41243
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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