Summary

Principal Investigator: Antonio Postigo

ICREA, Research professor
Transcriptional Regulation and Gene Expresion in Cancer Group
Department of Oncology and Hematology
IDIBAPS Biomedical Research Institute

This project aims to gain further insight into the mechanisms by which cancer cells in a colorectal tumor can escape the tumor, spread to adjacent healthy tissues, and eventually enter the blood stream to cause metastasis.

Project

Our investigations have revealed that proteins ZEB1 and ZEB2 play a key role in this process. Most of a colorectal tumor does not express ZEB1 and ZEB2, only those cells that have escaped from the tumor to metastasize do express the said proteins. Our experiments have shown that when a colorectal carcinoma tumor cell has ZEB1 and / or ZEB2 it becomes more mobile, more capable of migrating and with greater resistance to chemotherapy. Conversely, when ZEB1 and/or ZEB2 are eliminated from the tumor cell, it loses its migratory characteristics.The capacity of ZEB1 and ZEB2 to change a static tumor cell into a migratory and metastatic tumor cell is because both proteins are capable of activating the expression of other proteins that destroy the structure around

the tumor and thus, favor the metastasis of tumor cells. These studies will contribute in the future to better diagnosis and prognosis by associating ZEB1 and ZEB2 expression to stronger tumor aggressiveness and metastatic capacity. They will also allow creating new approaches in the treatment of colorectal cancer by interfering with the expression and function of ZEB1 and ZEB2 to prevent migration of tumor cells from the tumor to surrounding tissues and thus reduce the possibility of metastasis.