Therapeutic advances in BIG3-PHB2 inhibition targeting the cross-talk between estrogen and growth factors in breast cancer
| Project/Area Number |
26461948
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YOSHIMARU Tetsuro 徳島大学, 先端酵素学研究所(プロテオ), 講師 (80424729)
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| Co-Investigator(Renkei-kenkyūsha) |
KATAGIRI Toyomasa 徳島大学, 先端酵素学研究所, 教授 (60291895)
MIYOSHI Yasuo 兵庫医科大学, 医学部, 教授 (50283784)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 内分泌療法耐性乳癌 / エストロゲン受容体 / 乳癌 / クロストーク / 内分泌療法耐性乳がん / 乳がん / アロマターゼ阻害剤 |
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| Outline of Final Research Achievements |
We demonstrated that specific inhibitor of the BIG3-PHB2 complex, which is a critical modulator in estrogen (E2) signaling, ERAP, leads to suppression of E2-dependent estrogen-signaling activation. Here, we report that ERAP has significant suppressive effects against synergistic activation caused by the cross-talk between E2 and growth factors associated with intrinsic or acquired resistance to endocrine-therapy in breast cancer cells. Importantly, combined treatment with ERAP and some known anti-estrogen led to a synergistic suppression of signaling that was activated by cross-talk between E2 and growth factors or HER2 amplification. Furthermore, BIG3 overexpression is strongly associated with poor prognosis of breast cancer.
Taken together, our findings suggest that the specific inhibition of BIG3-PHB2 is a novel potential therapeutic approach for the treatment of endocrine-resistant breast cancers activated by the cross-talk between E2 and growth factor signaling.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Stapled BIG3 helical peptide ERAP extends potent antitumor activity for breast cancer therapeutics.2017
Author(s)
Yoshimaru T, Aihara K, Komatsu M, Matsushita Y, Okazaki Y, Toyokuni S, Honda J, Sasa M, Miyoshi Y, Otaka A, Katagiri T
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Journal Title
Scientific Reports
Volume: 印刷中
Pages: 1821-1821
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A-kinase anchoring protein BIG3 coordinates oestrogen signaling in breast cancer cells2017
Author(s)
Yoshimaru T, Ono M, Bando Y, Chen YA, Mizuguchi K, Shima H, Komatsu M, Imoto I, Izumi K, Honda J, Miyoshi Y, Sasa M, Katagiri T
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Journal Title
Nature Communications
Volume: 印刷中
Pages: 15427-15427
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor.2017
Author(s)
Shikata Y, Yoshimaru T, Komatsu M, Katoh H, Sato R, Kanagaki S, Okazaki Y, Toyokuni S, Tashiro E, Ishikawa S, Katagiri T, Imoto M.
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Journal Title
Cancer Science
Volume: 108
Pages: 785-794
DOI
Description
Epub ahead of print
Related Report
Peer Reviewed / Open Access
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