Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development.
Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development.
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DOI：
10.1186/bcr3483
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Frank PG
中科院分区：
文献类型：
--
作者：
Danilo C;Gutierrez-Pajares JL;Mainieri MA;Mercier I;Lisanti MP;Frank PG
以前的研究已经确定胆固醇是乳腺癌发展的重要调节因子。高密度脂蛋白（HDL）及其细胞受体，清道夫受体B类I型（SR-BI）都参与细胞胆固醇稳态的调节，但它们在癌症中的功能仍有待确定。在本研究中，我们已经研究了HDL和SR-BI在乳腺癌细胞系中的细胞信号通路的调节和在小鼠异种移植模型中的肿瘤的发展中的作用。我们的数据表明，HDL能够刺激迁移，并可以激活两个人乳腺癌细胞系，MDA-MB-231和MCF 7的信号转导通路。此外，我们还表明，敲除HDL受体SR-BI会减弱两种细胞系中HDL诱导的磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（Akt）途径的激活。另外的研究表明，在不存在SR-BI的情况下，抑制PI 3 K途径而非丝裂原活化蛋白激酶（MAPK）途径可导致细胞增殖减少。重要的是，尽管SR-BI的敲低导致体外增殖和迁移减少，但它也导致体内肿瘤生长显著减少。最重要的是，我们还表明，SR-BI的药理学抑制可以减弱信号传导，并导致体外细胞增殖减少。总之，我们的数据表明，胆固醇酯通过HDL-SR-BI和Akt信号进入细胞增殖和迁移，并最终，肿瘤生长的调节中发挥重要作用。这些结果确定SR-BI是治疗乳腺癌的潜在靶点。
Previous studies have identified cholesterol as an important regulator of breast cancer development. High-density lipoprotein (HDL) and its cellular receptor, the scavenger receptor class B type I (SR-BI) have both been implicated in the regulation of cellular cholesterol homeostasis, but their functions in cancer remain to be established. In the present study, we have examined the role of HDL and SR-BI in the regulation of cellular signaling pathways in breast cancer cell lines and in the development of tumor in a mouse xenograft model. Our data show that HDL is capable of stimulating migration and can activate signal transduction pathways in the two human breast cancer cell lines, MDA-MB-231 and MCF7. Furthermore, we also show that knockdown of the HDL receptor, SR-BI, attenuates HDL-induced activation of the phosphatidylinositol 3-kinase (PI3K)/protein Kinase B (Akt) pathway in both cell lines. Additional investigations show that inhibition of the PI3K pathway, but not that of the mitogen-activated protein kinase (MAPK) pathway, could lead to a reduction in cellular proliferation in the absence of SR-BI. Importantly, whereas the knockdown of SR-BI led to decreased proliferation and migration in vitro, it also led to a significant reduction in tumor growth in vivo. Most important, we also show that pharmacological inhibition of SR-BI can attenuate signaling and lead to decreased cellular proliferation in vitro. Taken together, our data indicate that both cholesteryl ester entry via HDL-SR-BI and Akt signaling play an essential role in the regulation of cellular proliferation and migration, and, eventually, tumor growth. These results identify SR-BI as a potential target for the treatment of breast cancer.
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影响因子：
45.3
作者：
Kitahara, Cari M.;de Gonzalez, Amy Berrington;Samet, Jonathan M.
通讯作者：
Samet, Jonathan M.
DOI：
10.1093/jnci/djh216
发表时间：
2004-08-04
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Furberg, AS;Veierod, MB;Thune, I
通讯作者：
Thune, I
影响因子：
4.3
作者：
Bonuccelli, Gloria;Tsirigos, Aristotelis;Lisanti, Michael P.
通讯作者：
Lisanti, Michael P.
影响因子：
15.9
作者：
Assanasen, C;Mineo, C;Silver, DL
通讯作者：
Silver, DL
DOI：
10.1016/0006-291x(85)91847-9
发表时间：
1985-01-01
影响因子：
3.1
作者：
JOZAN, S;FAYE, JC;BAYARD, F
通讯作者：
BAYARD, F