MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion.
MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion.
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DOI：
10.18632/oncotarget.6577
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发表时间：
2016-01-12
期刊：
影响因子：
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通讯作者：
Angeloni D
中科院分区：
文献类型：
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作者：
Mariotti S;Barravecchia I;Vindigni C;Pucci A;Balsamo M;Libro R;Senchenko V;Dmitriev A;Jacchetti E;Cecchini M;Roviello F;Lai M;Broccoli V;Andreazzoli M;Mazzanti CM;Angeloni D
在细胞骨架动力学中，Mical(与CASL相互作用的分子)蛋白催化肌动蛋白的氧化还原反应，破坏F-肌动蛋白的稳定性。在这里，我们首次展示了MICAL2mRNA在侵袭性、低分化/未分化的原发人类上皮癌(胃和肾)中显著过度表达。免疫组织化学显示MICAL2阳性细胞在癌侵袭前沿和栓子内的转移癌细胞中，但在转移部位没有，这表明MICAL2在一组原发癌细胞亚群中的表达是打开的，似乎是从起源组织分离，进入栓子并移动到遥远的位置，并在定位于转移位置时被关闭。在体外，MICAL2基因敲除可导致人癌细胞间充质向上皮细胞转化、存活率降低、运动能力丧失和侵袭能力丧失。此外，MICAL2基因在MICAL2缺失细胞中的表达可诱导上皮细胞向间充质细胞转化。总之，我们的数据表明MICAL2的过度表达与癌症进展和转移性疾病有关。MICAL2可能是上皮细胞向间充质细胞转化的重要调节因子，因此有望成为抗转移治疗的靶点。
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.