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Png, Kim J; Yoshida, Mitsukuni; Zhang, Xiang H-F; Shu, Weiping; Lee, Hyeseung; Rimner, Andreas; Chan, Timothy A; Comen, Elizabeth; Andrade, Viktor P; Kim, Seok Won; King, Tari A; Hudis, Clifford A; Norton, Larry; Hicks, James; Massagué, Joan; Tavazoie, Sohail F
Genes & development, 2011-Feb-01, 2011-02-01, 20110201, Letnik: 25, Številka: 3Journal Article
Post-transcriptional regulators have emerged as robust effectors of metastasis and display deregulated expression through unknown mechanisms. Here, we reveal that the human microRNA-335 locus undergoes genetic deletion and epigenetic promoter hypermethylation in every metastatic derivative obtained from independent patients' malignant cell populations. Genetic deletion of miR-335 is a common event in human breast cancer, is enriched for in breast cancer metastases, and also correlates with ovarian cancer recurrence. We furthermore identify miR-335 as a robust inhibitor of tumor reinitiation. We thus implicate the miR-335 locus on 7q32.2 as the first selective metastasis suppressor and tumor initiation suppressor locus in human breast cancer.
