摘要
原文 | 英語 |
---|---|
頁(從 - 到) | 3770-3784 |
頁數 | 15 |
期刊 | Oncotarget |
卷 | 5 |
發行號 | 11 |
出版狀態 | 已發佈 - 2014 |
指紋
ASJC Scopus subject areas
- Oncology
- Medicine(all)
引用此文
Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. / Siu, Man Kit; Abou-Kheir, Wassim; Yin, Juan Juan; Chang, Yung Sheng; Barrett, Ben; Suau, Florent; Casey, Orla; Chen, Wei Yu; Fang, Lei; Hynes, Paul; Hsieh, Yao Yu; Liu, Yen Nien; Huang, Jiaoti; Kelly, Kathleen.
於: Oncotarget, 卷 5, 編號 11, 2014, p. 3770-3784.研究成果: 雜誌貢獻 › 文章
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TY - JOUR
T1 - Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance
AU - Siu, Man Kit
AU - Abou-Kheir, Wassim
AU - Yin, Juan Juan
AU - Chang, Yung Sheng
AU - Barrett, Ben
AU - Suau, Florent
AU - Casey, Orla
AU - Chen, Wei Yu
AU - Fang, Lei
AU - Hynes, Paul
AU - Hsieh, Yao Yu
AU - Liu, Yen Nien
AU - Huang, Jiaoti
AU - Kelly, Kathleen
PY - 2014
Y1 - 2014
N2 - Activation of EGFR signaling pathway leads to prostate cancer bone metastasis; however, therapies targeting EGFR have demonstrated limited effectiveness and led to drug resistance. miR-203 levels are down-regulated in clinical samples of primary prostate cancer and further reduced in metastatic prostate cancer. Here we show that ectopic miR-203 expression displayed reduced bone metastasis and induced sensitivity to tyrosine kinase inhibitors (TKIs) treatment in a xenograft model. Our results demonstrate that the induction of bone metastasis and TKI resistance require miR-203 down regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TKIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, our data showed that miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature. Our results support the existence of a miR-203, EGFR, TKIs resistance regulatory network in prostate cancer progression. We propose that the loss of miR-203 is a molecular link in the progression of prostate cancer metastasis and TKIs resistance characterized by high EGFR ligands output and anti-apoptotic proteins activation.
AB - Activation of EGFR signaling pathway leads to prostate cancer bone metastasis; however, therapies targeting EGFR have demonstrated limited effectiveness and led to drug resistance. miR-203 levels are down-regulated in clinical samples of primary prostate cancer and further reduced in metastatic prostate cancer. Here we show that ectopic miR-203 expression displayed reduced bone metastasis and induced sensitivity to tyrosine kinase inhibitors (TKIs) treatment in a xenograft model. Our results demonstrate that the induction of bone metastasis and TKI resistance require miR-203 down regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TKIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, our data showed that miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature. Our results support the existence of a miR-203, EGFR, TKIs resistance regulatory network in prostate cancer progression. We propose that the loss of miR-203 is a molecular link in the progression of prostate cancer metastasis and TKIs resistance characterized by high EGFR ligands output and anti-apoptotic proteins activation.
KW - Bone metastasis
KW - Epidermal growth factor receptor (EGFR)
KW - KRAS
KW - miR-203
KW - Prostate cancer
KW - Tyrosine kinase inhibitors (TKIs) resistance
UR - http://www.scopus.com/inward/record.url?scp=84903539754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903539754&partnerID=8YFLogxK
M3 - Article
C2 - 25004126
AN - SCOPUS:84903539754
VL - 5
SP - 3770
EP - 3784
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 11
ER -