LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway

// Xiaoyan Li 1,2,* , Qifeng Yang 1,2,* , Haiyang Yu 1 , Lihua Wu 1,3 , Yuhan Zhao 1 , Cen Zhang 1 , Xuetian Yue 1 , Zhen Liu 1 , Hao Wu 1 , Bruce G. Haffty 1 , Zhaohui Feng 1 , Wenwei Hu 1,4 1 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey, New Brunswick, NJ, USA 2 Department of Breast Surgery, Qilu Hospital, Shandong University, Ji’nan, China 3 First Affiliated Hospital, Zhejiang University, Hangzhou, China 4 Department of Pharmacology, Rutgers State University of New Jersey, New Brunswick, NJ, USA * These authors contributed equally to this work Correspondence: Wenwei Hu, email: // Zhaohui Feng, email: // Keywords : LIF, breast cancer, AKT, mTOR, metastasis Received : January 17, 2014 Accepted : February 9, 2014 Published : February 15, 2014 Abstract 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.