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

Oncotarget. 2014 Feb 15;5(3):788-801. doi: 10.18632/oncotarget.1772.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Proliferation
  • Female
  • Heterografts
  • Humans
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*


  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • MTOR protein, human
  • TOR Serine-Threonine Kinases