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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.
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.
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.
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.
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?