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Page 14 of 16 Tu et al. J Cancer Metastasis Treat 2018;4:58 I http://dx.doi.org/10.20517/2394-4722.2018.67

In conclusion, until recently, metabolic reprogramming in the context of metastatic dissemination has been
largely unexplored in breast cancer. In the present study, a model of spontaneous metastatic breast cancer
was used to identify metabolic alterations involved in breast cancer progression. The highly metastatic MDA-
MB-231HM.LNm5 line displayed higher glycolytic activity and elevated oxidative phosphorylation compared
to the parental MDA-MB-231 line, despite reduced proliferative ability. We also showed that this enhanced
metabolic rate is only partially reflected by transcript levels of relevant metabolic regulators. Consideration
of protein translation, and post-translational modifications, may provide further insight into the molecular
alterations underlying the elevated glycolysis and oxidative phosphorylation in cells with higher metastatic
capacity. Characterization of the metabolic changes correlated to enhance metastatic potential would deepen
knowledge of metastatic mechanisms, and could facilitate the development of new strategies for therapeutic
interventions and clinical management of patients with metastatic breast cancer.

DECLARATIONS
Authors’ contributions
Derived the MDA-MB-231HM.LNm5 line, generated the reporter gene tagged MDA-MB-231 and MDA-MB-
231HMLNm5 lines: Johnstone CN
Conducted the Seahorse XF assays and contributed to the analysis and interpretation of the data: Ryall JG
Conducted the RNA-seq library preparation: Keenan CR
Analysed the FASTQ files from RNA sequencing: López-Campos GH
Conducted the majority of the experiments in the study, performed data analysis and interpretation, and
drafted the article: Tu Y
Contribution to conception and design of the study: Tu Y, Johnstone CN, Stewart AG
Major contributor to the conception and design of described work, contributed to writing and editing of the
manuscript, and will be the guarantor for this article: Stewart AG

Availability of data and materials
The datasets generated during and/or analysed during the current study are available from the correspond-
ing author on reasonable request.

Financial support and sponsorship
This work was supported by the National Health and Medical Research Council of Australia (1059655,
1023185).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

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