title: Lessons from tumor reversion for cancer treatment.
abstract: OBJECTIVE
  Tumor reversion is the biological process by which highly tumorigenic cells lose at great extent or entirely their malignant phenotype. The purpose of our research is to understand the molecular program of tumor reversion and its clinical application. We first established biological models of reversion, which was done by deriving revertant cells from different tumors. Secondly, the molecular program that could override the malignant phenotype was assessed. Differential gene-expression profiling showed that at least 300 genes are implicated in this reversion process such as SIAH-1, PS1, TSAP6, and, most importantly, translationally controlled tumor protein (TPT1/TCTP). Decreasing TPT1/TCTP is key in reprogramming malignant cells, including cancer stem cells.
  
  
  RESULTS
  Recent findings indicate that TPT1/TCTP regulates the P53-MDM2-Numb axis. Notably, TPT1/TCTP and p53 are implicated in a reciprocal negative-feedback loop. TPT1/TCTP is a highly significant prognostic factor in breast cancer. Sertraline and thioridazine interfere with this repressive feedback by targeting directly TPT1/TCTP and inhibiting its binding to MDM2, restoring wildtype p53 function. Combining sertraline with classical drugs such as Ara-C in acute myeloid leukemia may be also beneficial.
  
  
  CONCLUSIONS
  In this review, we discuss some of these reversion pathways and how this approach could open a new route to cancer treatment.
authors.affiliation: CNRS-UMR 8113, LBPA, École Normale Supérieure, Cachan, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Amson
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
authors.forename: Adam
authors.initials: A
authors.lastname: Telerman
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics; D000090324:Tumor Protein, Translationally-Controlled 1; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D000970:Antineoplastic Agents; D014150:Antipsychotic Agents; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D016159:Tumor Suppressor Protein p53