HSD11β1 promotes EMT-mediated breast cancer metastasis
HSD11β1 promotes EMT-mediated breast cancer metastasis
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HSD11β1促进EMT介导的乳腺癌转移
DOI：
10.1101/2021.09.27.461934
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
and Hideki Makinoshima
中科院分区：
文献类型：
--
作者：
Joji Nakayama;Ami Maruyama;Takamasa Ishikawa;Tatsunori Nishimura;Sanae Yamanaka;Noriko Gotoh;Chisako Yamauchi;Tatsuya Onishi;Tomoyoshi Soga;Satoshi Fujii;and Hideki Makinoshima
甾体激素的生物合成异常和甾体激素受体的调节异常与乳腺癌的转移有关，但其机制尚不清楚。在这里，我们报告了一种应激激素产生酶，羟基类固醇（11-β）脱氢酶1（HSD 11 β1）促进乳腺癌转移。HSD 11 β1在71%的三阴性乳腺肿瘤中异位表达，并与较短的总生存期相关。HSD 11 β1通过诱导上皮向间质转化（EMT）显著促进乳腺癌转移;相反，对HSD 11 β1的药理学和遗传学抑制抑制乳腺癌细胞的转移进展。此外，由HSD 11 β1在乳腺癌细胞中产生的11-羟孕酮（11-OHP）通过诱导EMT而赋予非转移性乳腺癌细胞转移特性。我们发现过氧化物酶体激活受体α（PPAR-α）对HSD 11 β1和11 OHP驱动的EMT都是必不可少的。在表达HSD 11 β1的乳腺癌细胞上敲低PPAR-α诱导MET。综上所述，HSD 11 β1促进乳腺癌转移，有望成为抑制乳腺癌转移的新靶点。
Abnormal biosyntheses of steroid hormones and dysregulation of steroid hormone receptors contribute to breast cancer metastasis but the mechanisms of that are poorly understand. Here we report a stress hormone producing enzyme, Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11β1) promotes breast cancer metastasis. HSD11β1 was ectopically expressed in seventy-one percent of triple-negative breast tumors and correlated with shorter overall survival. HSD11β1 significantly promoted breast cancer metastasis through induction of epithelial-to-mesenchymal transition (EMT); conversely, pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic progression of breast cancer cells. Moreover, 11-hydroxyprogesterone (11-OHP) whom HSD11β1 produced in breast cancer cells, conferred metastatic properties on non-metastatic breast cancer cells through induction of EMT. We identified Peroxisome Proliferator-activated Receptor Alpha (PPAR-α) as essential for both HSD11β1 and 11OHP-driven EMT. Knockdown of PPAR-α induced MET on HSD11β1-expressing breast cancer cells. Taken together, HSD11β1 promotes breast cancer metastasis and would be a novel target for suppressing breast cancer metastasis.
新生儿中的 C11-氧 C19 和 C11-氧 C21 类固醇：血浆 11β-羟基雄烯二酮、11-酮睾酮和 11-酮孕酮的 UPC2-MS/MS 定量
影响因子：
2.7
作者：
Therina du Toit;M. Finken;H. Hamer;A. Heijboer;A. Swart
通讯作者：
A. Swart