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Towards decoding the coupled decision-making of metabolism and epithelial-to-mesenchymal transition in cancer

British Journal of Cancer volume 124, pages 1902–1911 (2021)Cite this article

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Abstract

Cancer cells have the plasticity to adjust their metabolic phenotypes for survival and metastasis. A developmental programme known as epithelial-to-mesenchymal transition (EMT) plays a critical role during metastasis, promoting the loss of polarity and cell–cell adhesion and the acquisition of motile, stem-cell characteristics. Cells undergoing EMT or the reverse mesenchymal-to-epithelial transition (MET) are often associated with metabolic changes, as the change in phenotype often correlates with a different balance of proliferation versus energy-intensive migration. Extensive crosstalk occurs between metabolism and EMT, but how this crosstalk leads to coordinated physiological changes is still uncertain. The elusive connection between metabolism and EMT compromises the efficacy of metabolic therapies targeting metastasis. In this review, we aim to clarify the causation between metabolism and EMT on the basis of experimental studies, and propose integrated theoretical–experimental efforts to better understand the coupled decision-making of metabolism and EMT.

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Fig. 1: Crosstalk between EMT and metabolism in cancer.
Fig. 2: Hypothetical coupling of EMT and metabolic reprogramming during the acquisition of stemness.
Fig. 3: A systematic pipeline to elucidate the connection between EMT and metabolic reprogramming.

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Authors and Affiliations

  1. Center for Theoretical Biological Physics, Rice University, Houston, TX, USA

    Dongya Jia, Shubham Tripathi, Madeline Galbraith, Youyuan Deng & José N. Onuchic

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Jun Hyoung Park, Kwang Hwa Jung, Sukjin Yang & Benny Abraham Kaipparettu

  3. Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, Karnataka, India

    Harsimran Kaur & Mohit Kumar Jolly

  4. PhD Program in Systems, Synthetic, and Physical Biology, Rice University, Houston, TX, USA

    Shubham Tripathi

  5. Center for Theoretical Biological Physics and Department of Physics, Northeastern University, Boston, MA, USA

    Shubham Tripathi & Herbert Levine

  6. Department of Physics and Astronomy, Rice University, Houston, TX, USA

    Madeline Galbraith & José N. Onuchic

  7. Applied Physics Graduate Program, Rice University, Houston, TX, USA

    Youyuan Deng

  8. Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Benny Abraham Kaipparettu

  9. Department of Chemistry, Rice University, Houston, TX, USA

    José N. Onuchic

  10. Department of Biosciences, Rice University, Houston, TX, USA

    José N. Onuchic

  11. Department of Bioengineering, Northeastern University, Boston, MA, USA

    Herbert Levine

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  1. Dongya Jia
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Contributions

D.J., B.A.K., J.N.O. and H.L. conceptualized the review. D.J., J.H.P., H.K., K.W.J., S.Y., S.T., M.G., Y.D. and M.K.J. contributed to writing early drafts of the paper. D.J., B.A.K., J.N.O. and H.L. revised the final version of the paper.

Corresponding authors

Correspondence to Dongya Jia, Benny Abraham Kaipparettu, José N. Onuchic or Herbert Levine.

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Competing interests

The authors declare no competing interests.

Funding information

This work is supported by the National Science Foundation (NSF) Center for Theoretical Biological Physics (NSF PHY-2019745) and NSF grants nos. PHY-1605817, PHY-1522550, and CHEM-1614101. J.N.O. is a CPRIT Scholar in Cancer Research. D.J. is supported by a training fellowship from the Gulf Coast Consortia, on the Computational Cancer Biology Training Program (CPRIT grant no. RP170593). M.G. is supported by the NSF GRFP no. 1842494. B.A.K. is supported by NIH grants nos. CA253445, CA234479, DK117001 and CA235113 and DOD grant no. W81XWH-18-1-0714. M.K.J. is supported by Ramanujan Fellowship awarded by Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India (SB/S2/RJN-049/2018).

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Jia, D., Park, J.H., Kaur, H. et al. Towards decoding the coupled decision-making of metabolism and epithelial-to-mesenchymal transition in cancer. Br J Cancer 124, 1902–1911 (2021). https://doi.org/10.1038/s41416-021-01385-y

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  • DOI: https://doi.org/10.1038/s41416-021-01385-y

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