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Invasion and metastasis: the elusive hallmark of cancer

Oncogene volume 39, pages 2024–2026 (2020)Cite this article

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In their seminal review published nearly two decades ago, Hanahan and Weinberg introduced the “hallmarks of cancer” and typified essential biological abilities that are acquired by human cancer [1], including sustained proliferative signaling, resistance to apoptosis, evading growth suppressors, induction of angiogenesis, enabling replicative immortality, and invasion and metastasis. Eleven years later, in 2011, the authors added two more emerging hallmarks, reprogramming of energy metabolism and evading immune destruction [2]. In their updated review, genomic instability and tumor-promoting inflammation were also added as enabling characteristics of tumorigenesis. Since then, several authors attempted to define the complexities of cancer biology in different ways and challenged the criteria for inclusion of specific hallmarks [3].

Metastatic dissemination of malignant cells is the main cause of cancer-related mortality. Metastasis is one of the most enigmatic features of cancer biology, and is a complex sequential and interrelated process leading to the formation of distant secondary tumors, collectively termed the invasion-metastasis cascade. The series of events is initiated by migration and local invasion of cells into the surrounding extracellular matrix. Subsequently, cells intravasate into the vasculature, survive the rigorous conditions within the bloodstream, arrest at distant sites, extravasate into the organ parenchyma, adapt to the new microenvironment to form dormant cells or multicellular micrometastases, and eventually thrive in the foreign milieu to establish clinically detectable macroscopic metastases [2].

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Acknowledgements

This work was supported by the Israel Cancer Association and Estee Lauder Companies (grant number 20180089), the Israel Science Foundation (grant number 1462/17), and the Israel Cancer Research Fund (grant number 17-902-AG) (to HG-H), and by Leir Foundation and the Ginzburg Foundation (to AOS). TM is supported by the Foulkes Foundation fellowship for MD/PhD students.

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  1. Cell Migration and Invasion Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel

    Tomer Meirson & Hava Gil-Henn

  2. Drug Discovery Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel

    Tomer Meirson & Abraham O. Samson

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  1. Tomer Meirson
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Correspondence to Tomer Meirson.

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Meirson, T., Gil-Henn, H. & Samson, A.O. Invasion and metastasis: the elusive hallmark of cancer. Oncogene 39, 2024–2026 (2020). https://doi.org/10.1038/s41388-019-1110-1

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