MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion

Sara Mariotti, Ivana Barravecchia, Carla Vindigni, Angela Pucci, Michele Balsamo, Rosaliana Libro, Vera Senchenko, Alexey Dmitriev, Emanuela Jacchetti, Marco Cecchini, Franco Roviello, Michele Lai, Vania Broccoli, Massimiliano Andreazzoli, Chiara M. Mazzanti, Debora Angeloni

Research output: Contribution to journalArticlepeer-review

Abstract

The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidationreduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy.

Original languageEnglish
Pages (from-to)1808-1825
Number of pages18
JournalOncotarget
Volume7
Issue number2
DOIs
Publication statusPublished - 2016

Keywords

  • Epythelial to mesenchymal transition
  • Gastric cancer
  • Kidney cancer
  • Metastasis
  • MICAL2

ASJC Scopus subject areas

  • Oncology

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