Metastasis is the primary cause of mortality in most cancer patients. The resurgence of interest in this topic has led to significant new insights and translational developments. The articles in this Focus on Migration and metastasis, together with some recent Research Highlights and the accompanying library of the most relevant recent publications from Nature Research, describe our current understanding of this field.
In recent years, new avenues of investigation have enhanced our understanding of the metastatic process. Furthermore, models are re-emerging and numerous pathways have been redefined with regard to their role in metastasis. For example, epithelial-mesenchymal transition confers embryonic stem cell-like properties to tumour cells, increasing their ability to disseminate, survive and grow at distant sites, and adding more credence to the idea that tumours take on embryonic features. In addition, the microenvironment surrounding both the primary tumour and metastases is regarded to be a prominent regulator of metastatic potential and might facilitate metastatic tropism. The generation of gene signatures that provide information about the propensity of a tumour to form metastases and where in the body they might occur should lead to informed and hence improved treatment for patients with metastatic disease. Indeed, recent evidence suggests that metastasis might in fact occur earlier than first realized, and so therapy aimed at inhibiting pathways that promote this process or those that enable re-expression of metastasis suppressor proteins are under intense development.
Foreword
Charting a course to a distant site
Mary J. C. Hendrix
doi:10.1038/nrc2626
Nature Reviews Cancer 9, 237 (2009)
Research Highlights
Metastasis: Oxidizing abnormalities
Gemma K. Alderton
doi:10.1038/nrc2624
Nature Reviews Cancer 9, 227 (2009)
Metastasis: CHIPping away at tumour progression
Sarah Seton-Rogers
doi:10.1038/nrc2623
Nature Reviews Cancer 9, 232-233 (2009)
Metastasis: A malignant mutation
Meera Swami
doi:10.1038/nrc2625
Nature Reviews Cancer 9, 233 (2009)
Migration: Calcium influx is moving
Nicola McCarthy
doi:10.1038/nrc2629
Nature Reviews Cancer 9, 230-231 (2009)
Metastasis: When good drugs do bad things
Sarah Seton-Rogers
doi:10.1038/nrc2632
Nature Reviews Cancer 9, 228-229 (2009)
Metastasis: Suppression by Snail
Meera Swami
doi:10.1038/nrc2631
Nature Reviews Cancer 9, 232-233 (2009)
Metabolism: Monitoring progression
Meera Swami
doi:10.1038/nrc2630
Nature Reviews Cancer 9, 229 (2009)
Reviews
Microenvironmental regulation of metastasis
Johanna A. Joyce & Jeffrey W. Pollard
doi:10.1038/nrc2618
Nature Reviews Cancer 9, 239-252 (2009)
Metastatic dissemination and growth at distant sites are influenced by cells of the tumour microenvironment. What roles do these cells have in the underlying processes that determine metastatic growth?
Learning therapeutic lessons from metastasis suppressor proteins
Steven Christopher Smith & Dan Theodorescu
doi:10.1038/nrc2594
Nature Reviews Cancer 9, 253-264 (2009)
Metastasis suppressors inhibit metastasis but not the development of a primary tumour. Many of these genes have now been identified, and the therapeutic potential of restoring metastasis suppressor function is beginning to be examined.
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
Kornelia Polyak & Robert A. Weinberg
doi:10.1038/nrc2620
Nature Reviews Cancer 9, 265-273 (2009)
Transitions between epithelial and mesenchymal states seem to promote tumour heterogeneity and metastasis. This Review discusses the connections between epithelial and mesenchymal transitions and the acquisition of stem cell-like phenotypes.
Metastasis: from dissemination to organ-specific colonization
Don X. Nguyen, Paula D. Bos & Joan Massagué
doi:10.1038/nrc2622
Nature Reviews Cancer 9, 274-284 (2009)
The natural history of metastasis — which appears to be cancer-type specific — varies by target organ, latency and severity. This Review discusses how organ speciation and the competence to colonize might develop.
Perspectives
The metastatic niche: adapting the foreign soil
Bethan Psaila & David Lyden
doi:10.1038/nrc2621
Nature Reviews Cancer 9, 285-293 (2009)
How are sites of metastases chosen? Accumulating evidence suggests that primary tumour cells and circulating tumour cells might facilitate changes to the microenvironment in target organs so that a pre-metastatic niche, ideal for engraftment, forms.
MicroRNAs — the micro steering wheel of tumour metastases
Milena S. Nicoloso, Riccardo Spizzo, Masayoshi Shimizu, Simona Rossi & George A. Calin
doi:10.1038/nrc2619
Nature Reviews Cancer 9, 293-302 (2009)
microRNAs have recently been shown to affect diverse processes involved in metastasis. How do microRNAs interfere with or promote metastasis, could they be used as predictive markers, and are they possible therapeutic targets?
Parallel progression of primary tumours and metastases
Christoph A. Klein
doi:10.1038/nrc2627
Nature Reviews Cancer 9, 302-312 (2009)
When, in tumour progression, might metastasis be initiated? This Perspective argues that tumour cells disseminate early in malignant progression of the primary tumour so that disseminated tumour cells evolve the traits to allow growth within the metastatic site independently from the primary tumour.
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