CAFs are activated α-SMA+ mesenchymal cells that can be derived from activated hepatic stellate cells, the pericyte of the liver and potentially from other cells sources.71–73 The prevalence of α-SMA+ CAFs in tumours correlates with poor clinical outcomes in CC patients.72, 74 Investigation of interactions between CAFs and tumour cells show that CAFs support many of the malignant features of CC including proliferation, migration and evasion of apoptosis via secreted factors.73 An example of this is paracrine Hedgehog (HH) signalling. Here, ACTA1 is linked to neoplasm.