TY - JOUR
T1 - MiR-30b/30d Regulation of GalNAc Transferases Enhances Invasion and Immunosuppression during Metastasis
AU - Gaziel-Sovran, Avital
AU - Segura, Miguel F.
AU - Di Micco, Raffaella
AU - Collins, Mary K.
AU - Hanniford, Douglas
AU - Vega-Saenz de Miera, Eleazar
AU - Rakus, John F.
AU - Dankert, John F.
AU - Shang, Shulian
AU - Kerbel, Robert S.
AU - Bhardwaj, Nina
AU - Shao, Yongzhao
AU - Darvishian, Farbod
AU - Zavadil, Jiri
AU - Erlebacher, Adrian
AU - Mahal, Lara K.
AU - Osman, Iman
AU - Hernando, Eva
N1 - Funding Information:
We thank members of the NYU Cancer Institute Genomics Facility for array analysis, and Dr. Cindy Loomis and members of the NYU Cancer Institute Histopathology and Immunohistochemistry Core Laboratories for tissue processing and histological stainings. We thank Drs. Dan Littman and Vijay Kuchroo for the FoxP3 -GFP mice. We are grateful to Elisa De Stanchina (MSKCC), Silvia Menendez, and Lisa Koetz for technical assistance, Chin-Siean Tay for IF stainings, and to Dr. Michelle Krogsgaard and members of her lab for discussions and technical assistance. This work was funded by the ConCerN Foundation, the Melanoma Research Foundation, the Marc Jacobs Campaign, and funds from the NIH-NCI Cancer Center Support Grant P30CA016087. L.K.M. is supported by a NIH 7 DP2 OD004711-02 grant. M.F.S. is supported by a National Cancer Center fellowship, and R.D.M. by an EMBO post-doctoral fellowship. The authors declare no conflict of interest.
PY - 2011/7/12
Y1 - 2011/7/12
N2 - To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential, shorter time to recurrence, and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data support a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immunosuppression.
AB - To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential, shorter time to recurrence, and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data support a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immunosuppression.
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U2 - 10.1016/j.ccr.2011.05.027
DO - 10.1016/j.ccr.2011.05.027
M3 - Article
C2 - 21741600
AN - SCOPUS:79960064599
VL - 20
SP - 104
EP - 118
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 1
ER -