TY - JOUR
T1 - MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion
AU - Mariotti, Sara
AU - Barravecchia, Ivana
AU - Vindigni, Carla
AU - Pucci, Angela
AU - Balsamo, Michele
AU - Libro, Rosaliana
AU - Senchenko, Vera
AU - Dmitriev, Alexey
AU - Jacchetti, Emanuela
AU - Cecchini, Marco
AU - Roviello, Franco
AU - Lai, Michele
AU - Broccoli, Vania
AU - Andreazzoli, Massimiliano
AU - Mazzanti, Chiara M.
AU - Angeloni, Debora
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Epythelial to mesenchymal transition
KW - Gastric cancer
KW - Kidney cancer
KW - Metastasis
KW - MICAL2
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UR - http://www.scopus.com/inward/citedby.url?scp=84957708795&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6577
DO - 10.18632/oncotarget.6577
M3 - Article
VL - 7
SP - 1808
EP - 1825
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 2
ER -