Abstract
JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As2O3) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As2O3 on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin αVβ3 signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma.
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Acknowledgements
This study was partially supported by the grants of Key Basic Research Project of Department of Education, Jiangsu Province (06KJA33023), the National Natural Science Foundation of China (30771829, 30930080), the Doctoral Training Program of Education Ministry (200803120001) to JZ and the Jiangsu Provincial Graduate Students Innovation Project (CX08B-181Z) to JB; and Canadian Institutes of Health Research (MOP-84559 and MOP-93810), Cancer Research Society and Canadian Dermatology Foundation to GL.
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Bai, J., Zhang, J., Wu, J. et al. JWA regulates melanoma metastasis by integrin αVβ3 signaling. Oncogene 29, 1227–1237 (2010). https://doi.org/10.1038/onc.2009.408
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DOI: https://doi.org/10.1038/onc.2009.408
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