LAUSR

At least 1/3 of all acquired solid cancers produce unusual cyst-like structures (CLSs , PGCCs) with simultaneous loss of p53 function. However, p53 deficiency or accumulated mutations are not the causes of aCLS cancers. The cause is the reversal, to unicellularity, of a metabolic stressed cell by activating silenced transition switches and ancestral gene networks inherited from early Metazoans. After reprogramming and transformation the cell-of-origin of cancer bypasses mitosis and forms the polyploid pCLS, the homemade pathogen of aCLS cancers. pCLS's daughter cells (microcells) generate the pretumorigenic cancer stem cell pool (pCSCs) that start in turn the unicellular cancer cell lineage containing reproductive and somatic sublines. While the reproductive subline gives rise to new autonomous aCLSs by asymmetric division and cyclic differentiation, the somatic subline grows aCLS free. In the course of cancer evolution, some of the somatic mutants convert to stem cell precursors (SCPs). Somatic SCPs transfer part of somatic mutations and epimutations to the genome of newly formed reproductive clones. In this way, subsequent generations of tumorigenic and metastatic CSCs are being produced. aCLS cancer development is neither chaotic nor deregulated it follows unicellular development patterns. The unicellular program is controlled by mechanisms from early eukaryotic evolution.