Figure 8: Establishment of a tumour cell mass from an early stage neoplasm. (a) Where the ratio of antiproliferative/proapoptotic (green triangle) to proproliferative/antiapoptotic (red triangle) signals/receptors is high, then a tumour will fail to establish and will remain as a stable neoplasm (e.g., NLT). (b) An unstable neoplasm forms where the ratio of antiproliferative/proapoptotic to proproliferative/antiapoptotic signals/receptors is low and the microenvironment is no longer capable of positively regulating tissue homeostasis. (c) When the microenvironmental signals are tipped in favour of aberrant E-cadherin expression (i.e., a proproliferative/antiapoptotic phenotype), the neoplasm becomes an established tumour cell mass due to proliferation of the CSCs and TACs. (d) Reorganisation of the tumour cell mass leads to the formation of new tumorigenic stem cell niches (shown in blue circles) which subsequently regulate CSC proliferation.