title: MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion.
abstract: The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction 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.
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, 56124 Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mariotti
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, 56124 Pisa, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Barravecchia
authors.affiliation: U.O.C. Anatomia Patologica, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, 53100 Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Vindigni
authors.affiliation: U.O.C. Anatomia Patologica, Azienda Ospedaliera Universitaria Pisana, 56100 Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Pucci
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, 56124 Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Balsamo
authors.affiliation: BIOS Doctoral School in Life Sciences, University of Pisa, 56124 Pisa, Italy.
authors.forename: Rosaliana
authors.initials: R
authors.lastname: Libro
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
authors.forename: Vera
authors.initials: V
authors.lastname: Senchenko
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Dmitriev
authors.affiliation: NEST, National Enterprise for nanoScience and nanoTechnology, CNR and Scuola Normale Superiore, 56127 Pisa, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Jacchetti
authors.affiliation: NEST, National Enterprise for nanoScience and nanoTechnology, CNR and Scuola Normale Superiore, 56127 Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cecchini
authors.affiliation: Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, 56124 Pisa, Italy.|Pisa Science Foundation, 56100 Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Lai
authors.affiliation: DIBIT H San Raffaele, 20132 Milan, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
authors.affiliation: Department of Biology, University of Pisa, 56127 Pisa, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Andreazzoli
authors.affiliation: Pisa Science Foundation, 56100 Pisa, Italy.
authors.forename: Chiara M
authors.initials: CM
authors.lastname: Mazzanti
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, 56124 Pisa, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Angeloni
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D009857:Oncogenes / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000096985:Calponins
chemical_list: D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D010088:Oxidoreductases; C587931:MICAL2 protein, human; D000096985:Calponins
keywords: MICAL2; epythelial to mesenchymal transition; gastric cancer; kidney cancer; metastasis