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Linking adiponectin and autophagy in the regulation of breast cancer metastasis

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Abstract

Adipokines within the tumor microenvironment may play important roles in regulating the early steps of breast cancer metastasis. Adiponectin (AdipoQ) is the most abundant adipokine and exists in multiple forms: full-length multimers (fAd) and a cleaved, globular isoform (gAd). While these isoforms are observed as having distinct biological properties, nearly all investigation into AdipoQ in breast cancer has focused on the antitumor roles of fAd, while mostly ignoring gAd. However, evidence from other disease settings suggests that gAd is linked to processes known to promote metastasis. Here, we discuss key areas in which knowledge about AdipoQ in breast cancer is lacking, expressly focusing on data suggesting that gAd is elevated in the microenvironment and may act directly on invasive breast cancer cells to support their initial metastatic progression. We discuss autophagy as a potential mechanism of action for this effect. Overall, given that AdipoQ and AdipoQ receptor agonists have been proposed as therapeutic strategies, it is necessary to better understand the various functions of these regulatory molecules in metastatic breast cancer. Doing so will help ensure the most effective approaches to treating this disease, for which there remain no curative options.

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Acknowledgments

We acknowledge Monica Lewis, Jianzhong Liu, Dr. James Cody, and Dr. Yi Li for their valuable discussions. The Hurst lab is funded by the American Cancer Society (RSG-11-259-01-CSM) and METAvivor Research and Support, Inc. Funding was also provided by the UAB Cancer Prevention and Control Training Program (R25 CA047888).

Conflict of Interest

The authors declare that they have no conflict of interests. This manuscript does not contain clinical studies or patient data.

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Authors and Affiliations

  1. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA

    Emily Falk Libby & Wendy Demark-Wahnefried

  2. Department of Pathology, University of Alabama at Birmingham, 1720 2nd Avenue South, Volker Hall G019A, Birmingham, AL, 35294-0019, USA

    Emily Falk Libby, Andra R. Frost & Douglas R. Hurst

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  1. Emily Falk Libby
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  2. Andra R. Frost
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  4. Douglas R. Hurst
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Correspondence to Douglas R. Hurst.

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Libby, E.F., Frost, A.R., Demark-Wahnefried, W. et al. Linking adiponectin and autophagy in the regulation of breast cancer metastasis. J Mol Med 92, 1015–1023 (2014). https://doi.org/10.1007/s00109-014-1179-5

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  • DOI: https://doi.org/10.1007/s00109-014-1179-5

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