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Energy metabolism and proliferation in pancreatic carcinogenesis

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Abstract

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer entity with a high proliferative potential. Uncontrolled cell proliferation is mediated by a number of core signaling pathways. Recently, novel data of PDAC biology suggest that these core signal pathways affect cell proliferation and metabolism simultaneously.

Methods

Here, we reviewed the literature on core metabolic signaling pathways in pancreatic carcinogenesis.

Results

Results obtained from mouse genetics and in vitro experiments have demonstrated the significance of the Kras, p53, c-Myc, and Lkb1 networks in the proliferation of pancreatic epithelial and cancer cells. At the same time, these major pathways also affect energy metabolism by influencing glucose and glutamine utilization. In particular, Kras-mediated metabolic changes seem to be directly involved in carcinogenesis. However, there is a lack of solid evidence on how metabolism and proliferation are connected in pancreatic carcinogenesis.

Conclusion

Understanding early and subtle changes in cellular metabolism of pancreatic epithelial—and specifically of acinar—cells, which accompany or directly influence malignant transformation and uncontrolled proliferation, will be paramount to define novel imaging and other modalities for earlier detection of PDAC.

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Acknowledgments

This study has in part been supported by a grant from the Else-Kröner-Fresenius-Stiftung (to CWM and JK) and from the European Union (EPC-TM-NET, within the FP7 program, to CWM, ME, and JK).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Surgery, Technische Universität München, Ismaningerstrasse 22, 81675, Munich, Germany

    Ivonne Regel, Bo Kong, Susanne Raulefs, Mert Erkan, Christoph W. Michalski & Jörg Kleeff

  2. Department of Surgery, Dortmund Hospital, 44139, Dortmund, Germany

    Mark Hartel

Authors
  1. Ivonne Regel
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  2. Bo Kong
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  3. Susanne Raulefs
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  4. Mert Erkan
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  5. Christoph W. Michalski
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  6. Mark Hartel
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  7. Jörg Kleeff
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Corresponding authors

Correspondence to Mark Hartel or Jörg Kleeff.

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Regel, I., Kong, B., Raulefs, S. et al. Energy metabolism and proliferation in pancreatic carcinogenesis. Langenbecks Arch Surg 397, 507–512 (2012). https://doi.org/10.1007/s00423-012-0933-9

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  • DOI: https://doi.org/10.1007/s00423-012-0933-9

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