The mTOR inhibitor rapamycin synergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells.
The mTOR inhibitor rapamycin synergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells.
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DOI：
10.1371/journal.pone.0097697
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sheng H
中科院分区：
文献类型：
--
作者：
Yan C;Wei H;Minjuan Z;Yan X;Jingyue Y;Wenchao L;Sheng H
ER/ her2阳性乳腺癌患者预后较差，对选择性雌激素受体调节剂反应较差；这可能是由于ER和HER2之间的串扰。脂肪酸合成酶（FASN）对乳腺癌细胞恶性表型的生存和维持至关重要。FASN、ER和HER2之间存在密切关系。我们假设FASN可能是ER/HER2阳性乳腺癌中通过PI3K/AKT/mTOR通路的ER/HER2串扰的下游效应因子。本研究提示PI3K/AKT/mTOR通路在ER/ her2阳性乳腺癌细胞中调控FASN表达，并证明mTOR抑制剂雷帕霉素可抑制FASN表达。Cerulenin是一种FASN抑制剂，可与雷帕霉素协同诱导ER/ her2阳性乳腺癌细胞凋亡，抑制细胞迁移和肿瘤发生。我们的研究结果表明，抑制mTOR-FASN轴是治疗ER/ her2阳性乳腺癌的一种有希望的新策略。
Patients with ER/HER2-positive breast cancer have a poor prognosis and are less responsive to selective estrogen receptor modulators; this is presumably due to the crosstalk between ER and HER2. Fatty acid synthase (FASN) is essential for the survival and maintenance of the malignant phenotype of breast cancer cells. An intimate relationship exists between FASN, ER and HER2. We hypothesized that FASN may be the downstream effector underlying ER/HER2 crosstalk through the PI3K/AKT/mTOR pathway in ER/HER2-positive breast cancer. The present study implicated the PI3K/AKT/mTOR pathway in the regulation of FASN expression in ER/HER2-positive breast cancer cells and demonstrated that rapamycin, an mTOR inhibitor, inhibited FASN expression. Cerulenin, a FASN inhibitor, synergized with rapamycin to induce apoptosis and inhibit cell migration and tumorigenesis in ER/HER2-positive breast cancer cells. Our findings suggest that inhibiting the mTOR-FASN axis is a promising new strategy for treating ER/HER2-positive breast cancer.
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影响因子：
4
作者：
Hayashi, Satoshi;Kitada, Masahiro;Hirata, Satoshi
通讯作者：
Hirata, Satoshi
DOI：
10.1073/pnas.0403390101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Menendez, JA;Vellon, L;Lupu, R
通讯作者：
Lupu, R
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1158/1078-0432.ccr-09-1665
发表时间：
2009-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Miller TW;Forbes JT;Shah C;Wyatt SK;Manning HC;Olivares MG;Sanchez V;Dugger TC;de Matos Granja N;Narasanna A;Cook RS;Kennedy JP;Lindsley CW;Arteaga CL
通讯作者：
Arteaga CL
影响因子：
8
作者：
Menendez, JA;Oza, BP;Lupu, R
通讯作者：
Lupu, R