LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway.
LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway.
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DOI：
10.18632/oncotarget.1772
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发表时间：
2014-02-15
期刊：
影响因子：
--
通讯作者：
Hu W
中科院分区：
文献类型：
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作者：
Li X;Yang Q;Yu H;Wu L;Zhao Y;Zhang C;Yue X;Liu Z;Wu H;Haffty BG;Feng Z;Hu W
白血病抑制因子（Leukemia inhibitory factor， LIF）是一种多功能细胞因子蛋白。LIF在肿瘤发生中的作用尚不清楚。在这里，我们发现LIF促进乳腺癌的肿瘤发生和转移。LIF在体外促进乳腺癌细胞增殖和不依赖锚定生长，在体内促进异种乳腺肿瘤的生长。在体外，LIF还促进乳腺癌细胞的侵袭和迁移以及体内乳腺癌的转移。我们发现LIF激活AKT-mTOR信号通路，促进乳腺癌的发生和转移。抑制AKT活性可在很大程度上阻断LIF对mTOR通路的激活，提示LIF通过AKT激活mTOR通路。抑制AKT活性和抑制mTOR活性在很大程度上阻断了LIF对肿瘤发生转移的促进作用。此外，在乳腺癌患者中，LIF的过表达与较差的无复发生存率显著相关。综上所述，我们的数据强烈表明，LIF在乳腺癌的发生和转移中起着重要作用，可能是乳腺癌的重要预后指标。
Leukemia inhibitory factor (LIF) is a multi-functional cytokine protein. The role of LIF in tumorigenesis is not well-understood. Here, we found that LIF promotes tumorigenesis and metastasis of breast cancer. LIF promotes cell proliferation and anchorage-independent growth of breast cancer cells in vitro, and the growth of xenograft breast tumors in vivo. LIF also promotes invasion and migration of breast cancer cells in vitro and metastasis of breast cancer in vivo. We found that LIF activates the AKT-mTOR signaling pathway to promote tumorigenesis and metastasis of breast cancer. Inhibiting the AKT activity can largely block the activation of the mTOR pathway by LIF, suggesting that LIF activates the mTOR pathway through AKT. Inhibiting the AKT activity as well as inhibiting the mTOR activity largely block the promoting effect of LIF on tumorigenesis and metastasis. Furthermore, overexpression of LIF is significantly associated with a poorer relapse free survival in breast cancer patients. Taken together, our data strongly suggest that LIF plays an important role in the tumorigenesis and metastasis of breast cancer, and could be an important prognostic marker for breast cancer.