期刊
ONCOTARGET
卷 5, 期 3, 页码 788-801出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1772
关键词
LIF; breast cancer; AKT; mTOR; metastasis
资金
- National Institutes of Health (NIH) [1R01CA160558-01]
- Department of Defense [W81XWH-10-1-0435]
- Ellison Foundation
- New Jersey Health foundation
- Rutgers Cancer Institute of New Jersey
- NIH [1R01CA143204-01]
- NJCCR
- Breast Cancer Research Foundation
- NATIONAL CANCER INSTITUTE [R01CA160558, R01CA143204, P30CA072720] Funding Source: NIH RePORTER
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.
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