Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow

Rachelle W. Johnson, Elizabeth C. Finger, Monica M. Olcina, Marta Vilalta, Todd Aguilera, Yu Miao, Alyssa R. Merkel, Joshua R. Johnson, Julie A. Sterling, Joy Y. Wu, Amato J. Giaccia

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84 Scopus citations

Abstract

Breast cancer cells frequently home to the bone marrow, where they may enter a dormant state before forming a bone metastasis. Several members of the interleukin-6 (IL-6) cytokine family are implicated in breast cancer bone colonization, but the role for the IL-6 cytokine leukaemia inhibitory factor (LIF) in this process is unknown. We tested the hypothesis that LIF provides a pro-dormancy signal to breast cancer cells in the bone. In breast cancer patients, LIF receptor (LIFR) levels are lower with bone metastases and are significantly and inversely correlated with patient outcome and hypoxia gene activity. Hypoxia also reduces the LIFR:STAT3:SOCS3 signalling pathway in breast cancer cells. Loss of the LIFR or STAT3 enables otherwise dormant breast cancer cells to downregulate dormancy-, quiescence- and cancer stem cell-associated genes, and to proliferate in and specifically colonize the bone, suggesting that LIFR:STAT3 signalling confers a dormancy phenotype in breast cancer cells disseminated to bone.

Original languageEnglish (US)
Pages (from-to)1078-1089
Number of pages12
JournalNature cell biology
Volume18
Issue number10
DOIs
StatePublished - Sep 28 2016

ASJC Scopus subject areas

  • Cell Biology

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    Johnson, R. W., Finger, E. C., Olcina, M. M., Vilalta, M., Aguilera, T., Miao, Y., Merkel, A. R., Johnson, J. R., Sterling, J. A., Wu, J. Y., & Giaccia, A. J. (2016). Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nature cell biology, 18(10), 1078-1089. https://doi.org/10.1038/ncb3408