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  • Review Article
  • Published:

Obesity and cancer—mechanisms underlying tumour progression and recurrence

Nature Reviews Endocrinology volume 10, pages 455–465 (2014)Cite this article

Subjects

Key Points

  • The current notion that obesity is a major risk factor for development of, and mortality associated with a subset of cancers is well appreciated; however, detailed mechanistic insights underlying this relationship are still lacking

  • Adipose tissues that influence functions of cancer cells, such as growth, metastasis and recurrence, are an integral part of the tumour microenvironment

  • Heterotypic signals between cancer-associated adipocytes and cancer cells provide a permissive niche for the growth and metastasis of tumours

  • Obesity-related inflammation is a plausible link between obesity and cancer

  • Metabolic symbiosis between stromal adipocytes and cancer cells may account, in part, for the link between obesity and cancer

  • The effects of obesity on cancer progression might be specifically curbed through weight-loss interventions, such as exercise or medication

Abstract

Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment.

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Figure 1: Reciprocal signalling between cancer-associated adipocytes and cancer cells.
Figure 2: Potential consequences of obesity-induced dysfunction of adipose tissue on tumour initiation, progression and recurrence.

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Acknowledgements

The authors' research was supported by NIH Grants R01-DK55758, R01-DK099110 (to P.E.S.) and P01-DK088761 (to P.E.S. and D.J.C.). J.P.'s research was supported by a fellowship from the US Department of Defence (USAMRMC BC085909) and 2014 research fund (1.130088.01) of Ulsan National Institute of Science and Technology. T.S.M.'s work was supported by NIH Training Grant T32-GM083831.

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  1. Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST Street, Ulsan, 689–798, South Korea

    Jiyoung Park

  2. Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390, TX, USA

    Thomas S. Morley, Min Kim, Deborah J. Clegg & Philipp E. Scherer

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  1. Jiyoung Park
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J.P. and T.S.M. contributed equally to this article. J.P., T.S.M., D.J.C. and P.E.S undertook discussions of the article content, writing, and review or editing of the manuscript before submission. In addition, M.K. contributed to discussions of the content and writing the manuscript.

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Correspondence to Philipp E. Scherer.

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Park, J., Morley, T., Kim, M. et al. Obesity and cancer—mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol 10, 455–465 (2014). https://doi.org/10.1038/nrendo.2014.94

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