For clonal outgrowth at metastatic sites, as for final developmental cellular differentiation, EMT reversion such as mesenchymal to epithelial transition (MET) is required [ 76, 77].
To acquire a migratory/invasive phenotype for metastatic progression, tumor cells activate the developmental EMT program.
Many questions remain about which aspects of EMT promote metastatic dissemination and how cancers hijack developmental EMT to progress.
The similarity of genetic controls and biochemical mechanisms underlying the acquisition of the invasive phenotype and the subsequent systemic spread of cancer cells highlights that tumor cells usurp the developmental pathways for their metastatic dissemination.
Findings typically fall into six categories: skin lesions, congenital and developmental anomalies, infectious, inflammatory and metastatic lymphadenopathy, post-operative changes, benign neoplasms and extra-axillary masses (Table 1).
Our findings, that loss of Mena decreases ductal branching and TEB formation (both considered to be invasive processes in the developing mammary gland), and blunts invasion during metastatic progression, suggests that Mena's role in developmental invasion is recapitulated during metastatic progression.
In cancer research, cancer biology should be linked more closely with developmental biology so that the non-metastatic linkages between many "unusual" multi-organ cancers can be found by their underlying cell lineage links in development.
Accumulating evidence suggests that aberrant activation of the EMT developmental programme contributes to tumour initiation, invasion, metastatic dissemination, and acquisition of therapeutic resistance (Yang and Weinberg, 2008; Acloque et al, 2009; Kalluri and Weinberg, 2009; Thiery et al, 2009).
The mammalian TSPO localizes to the mitochondrial outer membrane but during fast cell proliferation, such as metastatic processes, it relocates to the nuclear membrane, suggesting developmental control of its sub-cellular localization [ 46].
Thus, multiple factors in addition to MITF may be responsible for the differential expression of developmental genes associated with the invasive potential of metastatic melanoma cells.
