PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnt high Metastatic Colon Cancer Cells

• DOI: 10.1016/j.celrep.2014.08.041
• Publication Date: 2014-09-18T17:27:31Z
• Authors: Simone Ragusa; Jianpin Cheng; Konstantin I. Ivanov; Nadine Zangger; Fatih Ceteci; Jeremiah Bernier-...; Stavros Milatos; Jean-Marc Joseph; Stephane Tercier; Hanifa Bouzourene; Fredrik T. Bosman; Igor Letovanec; Giancarlo Marra; Michel Gonzalez; Patrizia Cammareri; Owen J. Sansom; Mauro Delorenzi; Tatiana V. Petrova
• Keywords: Metabolic adaptation

The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained understanding its role tumor initiation. However, mechanisms metastatic outgrowth cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation survival cells regulated by target oncogenic signaling, homeobox transcription factor PROX1, expressed subpopulation colon progenitor/stem cells. identify direct PROX1 genes show repression pro-apoptotic member BCL2 family, BCL2L15, important for PROX1+ under stress. inactivation after establishment metastases prevented further growth lesions. Furthermore, autophagy inhibition efficiently targeted cells, suggesting potential therapeutic approach. These data as key regulator transcriptional network contributing to cancer.