Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jan 28;16(1):301.
doi: 10.1186/bcr3608.

Targeting RET-interleukin-6 crosstalk to impair metastatic dissemination in breast cancer

Andrea Morandi, Clare M Isacke

Targeting RET-interleukin-6 crosstalk to impair metastatic dissemination in breast cancer

Andrea Morandi et al. Breast Cancer Res. .

Abstract

RET (rearranged during transfection) is a receptor tyrosine kinase overexpressed in a subset of oestrogen receptor (ER)-positive breast cancers whose expression is regulated by ER signalling. The article from the Hynes group has reported for the first time that RET expression can also be regulated by the inflammatory cytokine IL-6. Importantly, RET and IL-6 interact at a functional level to control migration and the metastatic potential of ER-positive breast cancer cells, in a process that is mediated by FAK activation. Further, targeting RET with receptor tyrosine kinase inhibitors was reported to be more effective than endocrine therapies in impairing metastatic dissemination in vivo, thereby indicating a level of RET regulation that is independent of ER.

PubMed Disclaimer

Figures

Figure 1
Figure 1
RET–IL-6 interaction mediates breast cancer cell motility. (A) GDNF binds to GFRα1 and induces RET activation. IL-6-mediated IL-6 receptor (IL6R) activation leads to co-receptor gp130 phosphorylation (P). (B) RET directly interacts with and activates FAK, while IL6R/gp130 activation induces JAK phosphorylation. Data presented by Gattelli and colleagues suggest a transient interaction between the IL6R:JAK and RET:FAK activated complexes that form in response to IL-6 and GDNF treatment, respectively [7]. (C) RET and FAK are essential to IL-6:JAK-mediated STAT3 activation underpinning the observed requirement for RET in IL-6-stimulated breast cancer cell migration and invasion.
See this image and copyright information in PMC

References

    1. Esseghir S, Todd SK, Hunt T, Poulsom R, Plaza-Menacho I, Reis-Filho JS, Isacke CM. A role for glial cell derived neurotrophic factor induced expression by inflammatory cytokines and RET/GFR alpha 1 receptor up-regulation in breast cancer. Cancer Res. 2007;67:11732–11741. doi: 10.1158/0008-5472.CAN-07-2343. - DOI - PubMed
    1. Boulay A, Breuleux M, Stephan C, Fux C, Brisken C, Fiche M, Wartmann M, Stumm M, Lane HA, Hynes NE. The Ret receptor tyrosine kinase pathway functionally interacts with the ERα pathway in breast cancer. Cancer Res. 2008;68:3743–3751. doi: 10.1158/0008-5472.CAN-07-5100. - DOI - PubMed
    1. Morandi A, Plaza-Menacho I, Isacke CM. RET in breast cancer: functional and therapeutic implications. Trends Mol Med. 2011;17:149–157. doi: 10.1016/j.molmed.2010.12.007. - DOI - PubMed
    1. Morandi A, Martin LA, Gao Q, Pancholi S, Mackay A, Robertson D, Zvelebil M, Dowsett M, Plaza-Menacho I, Isacke CM. GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013;73:3787–3795. - PMC - PubMed
    1. Plaza-Menacho I, Morandi A, Robertson D, Pancholi S, Drury S, Dowsett M, Martin LA, Isacke CM. Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene. 2010;29:4648–4657. doi: 10.1038/onc.2010.209. - DOI - PubMed

Publication types

MeSH terms