methods and any associated references are available in the online version of the paper at http://www.nature.com / naturemedicine/. note : 
 supplementary information 
 is available on the nature medicine website .
 cancer stem cells ( cscs ) or tumor progenitor cells are involved in tumor progression and metastasis1 . 
 micrornas ( mirnas ) regulate both normal stem cells and cscs25 and mirna dysregulation has been implicated in tumorigenesis6 . 
 cscs in many tumors , including cancers of the breast7 , pancreas8 , head and neck9 , colon10,11 , small intestine12 , liver13 , stomach14 , bladder15 , and ovary16 have been identified using adhesion molecule cd44 , either individually or in combination with other marker(s ) . 
 prostate cancer ( pca ) stem / progenitor cells with enhanced clonogenic17 and tumor - initiating and metastatic18,19 capacities are also enriched in the cd44 + cell population , but whether mirnas regulate the cd44 + pca cells and pca metastasis remains unclear . here 
 we show , through expression analysis , that mir-34a , a p53 target2024 , was under - expressed in cd44 + pca cells purified from xenograft and primary tumors . 
 enforced expression of mir-34a in bulk pca cells inhibited clonogenic expansion and tumor development . 
 mir-34a re - expression in cd44 + pca cells blocked whereas mir-34a antagomirs in cd44 pca cells promoted tumor regeneration and metastasis . 
 systemically delivered mir-34a inhibited pca metastasis and extended animal survival . of significance , cd44 was identified and validated as a direct and functional target of mir-34a and cd44 knockdown phenocopied mir-34a over - expression in inhibiting pca regeneration and metastasis . 
 our study reveals mir-34a as a critical negative regulator of cd44 + pca cells and establishes a strong rationale for developing mir-34a as a novel therapeutic against prostate cscs . 
METHODS
Supplementary Material