Genes of ancient microtubule-stabilizing proteins traveled through pre-Cambrian Echinoidea to advanced life forms of dry land and ended up in the human genome as the fusion oncogenes-oncoproteins eml1/EML1-abl/ABL, and eml4/EML4-alk/ALK


  • J G Sinkovics Department of Molecular Medicine, The University of South Florida Morsani College of Medicine, The Cancer Institute, St. Joseph’s Hospital, Tampa FL, USA



sea cucumbers, microtubule-associated proteins, oncogenes-oncoproteins, EML1/4 proteins


The genes eml1/4 of the Echinodermata microtubule-stabilizing gene product-like 1/4 proteins
EML1/4 of the sea cucumbers (Holothuroidea) traveled through the evolutionary scale up to the human genome. Human cells malignantly transformed by oncogenes abl or alk enlist the protein products EML1/4 for the activation and protection of the gene product oncoproteins ABL or ALK against destruction by ubiquitination, and for gaining virulence and chemotherapy resistance. Neither the abl nor the alk genes act as oncogenes without fusion with another particular gene, such as eml1/4 in this case. A large number of ancient but conserved gene product proteins chaperon, protect and enhance oncoproteins. These mechanisms indicate that ancient cell survival pathways exist conserved in the genomes of advanced multicellular diplo- and triploblastic hosts (including Homo). These genomic pathways are on special occasions constitutively reactivated in extant cells undergoing transformations for survival under adverse circumstances. Extant cells under threat react by re-living scenarios that characterized life forms in the primordial physico-chemical universe. In the clinical practice these cells are recognized as chemoradiotherapy-resistant cancer cells undergoing a process of retrograde immortalization.