Metastatic niche functions and therapeutic opportunities

Metastasis is an inefficient process, especially during colonization at a distant organ. This bottleneck underlies the importance of the metastatic niche for seeding and outgrowth of metastases. Here, we classify the common functions of different metastatic niches: anchorage, survival support, protection from external insults, licensing proliferation and outgrowth. We highlight the emerging role of the metastatic niche in maintaining cancer stemness and promoting immune evasion, and discuss therapeutic opportunities against the metastatic niche

A molecular portrait of epithelial–mesenchymal plasticity in prostate cancer associated with clinical outcome

The propensity of cancer cells to transition between epithelial and mesenchymal phenotypic states via the epithelial–mesenchymal transition (EMT) program can regulate metastatic processes, cancer progression, and treatment resistance. Transcriptional investigations using reversible models of EMT, revealed the mesenchymal-to-epithelial reverting transition (MErT) to be enriched in clinical samples of metastatic castrate resistant prostate cancer (mCRPC). From this enrichment, a metastasis-derived gene signature was identified that predicted more rapid cancer relapse and reduced survival across multiple human carcinoma types. Additionally, the transcriptional profile of MErT is not a simple mirror image of EMT as tumour cells retain a transcriptional “memory” following a reversible EMT. This memory was also enriched in mCRPC samples. Cumulatively, our studies reveal the transcriptional profile of epithelial–mesenchymal plasticity and highlight the unique transcriptional properties of MErT. Furthermore, our findings provide evidence to support the association of epithelial plasticity with poor clinical outcomes in multiple human carcinoma types