Comment[ArrayExpressAccession] E-GEOD-24868 Public Release Date 2012-07-23 Investigation Title Suppression of major attributes of tumor-initiating cells through epithelial-mesenchymal transition Comment[Submitted Name] Suppression of major attributes of tumor-initiating cells through epithelial-mesenchymal transition Experiment Description Malignant progression in cancer has been associated with the emergence of populations of tumor-initiating cells (TIC) endowed with capabilities for unlimited self-renewal, survival under stress and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by the genetic program known as epithelialmesenchymal transition (EMT) may be an essential step in the evolution of neoplastic cells into fully metastatic populations. A widely accepted paradigm is that EMT potentiates tumor cell self-renewal and metastatic behaviour. Here we describe a cellular model in which a clonal population enriched in TIC expresses a genetic program distinct from a second population with traits of stable EMT, and in which both populations cooperate for enhanced local invasiveness and metastasis. Induction of the TIC-enriched population to undergo EMT by several stimuli or by constitutive overexpression of the transcription factor SNAI1 engaged a mesenchymal program while suppressing the CSC program. This suggests that TIC and EMT, contrary to current paradigms, correspond to alternative states. Furthermore, diffusible factors secreted by the population with EMT traits also induced mesenchymal reprogramming of the population enriched in CSCs. Local invasiveness in vitro and lung colonization in vivo of the TIC-enriched population was enhanced by co-injection with the EMT-trait population, and expanded the range of organs to which it metastasized. Thus, in our model, relatively stable TIC and EMT phenotypes reflect alternative genetic programs expressed by distinct clonal populations. We also suggest that dynamic cooperation between tumor subpopulations displaying either TIC or EMT traits may be a general mechanism driving local invasiveness and metastasis. The complete database comprised the expression measurements of 54 675 genes for PC-3/Mc (n=3) and PC-3/S (n=3) Date of Experiment Term Source Name EFO Term Source Version Term Source File http://www.ebi.ac.uk/efo/efo.owl Person Last Name Lozano Celià-Terrassa Meca-Cortés Mateo de Paz Rubio Arnal-Estapé Ell Bermudo Díaz Guerra-Rebollo Lozano Estarás Ulloa Álvarez-Simón Milà Vilella Paciucci Martínez-Balbás de Herreros Gomis Kang Blanco Fernández Thomson Person First Name Juanjo A O F A N A B R A M J C C D J R R M A R Y J P T Person Mid Initials M J J G R L M Person Email juanjo.lozano@ciberehd.org Person Affiliation CIBEREHD Person Phone Person Fax Person Address Plataforma de Bioinformatica, CIBEREHD, C/ Rosselló 153 , Barcelona, Spain Person Roles submitter Person Roles Term Source REF Person Roles Term Accession Number Normalization Type Normalization Term Accession Number Normalization Term Source REF Replicate Type Replicate Term Accession Number Replicate Term Source REF Experimental Design Experimental Design Term Accession Number Experimental Design Term Source REF Quality Control Type Quality Control Term Accession Number Quality Control Term Source REF Protocol Name P-GSE24868-1 P-GSE24868-5 P-GSE24868-4 P-GSE24868-2 P-GSE24868-3 P-GSE24868-6 Protocol Description ID_REF =
VALUE = RMA log2 signal The labelled arrays were scanned with a Gene chip scanner 3000. Standard Affymetrix protocol Cells were grown to 70-80% confluence, lysed and RNA isolated with the RNeasy Kit (Qiagen, Hilden, Germany) standard Affymetrix protocol Data processing cel files were normalized with 'rma' function of the Bioconductor package (v2.4) 'affy' in R.2.9.1 Protocol Software Protocol Hardware Protocol Contact Protocol Type bioassay_data_transformation image_aquisition hybridization nucleic_acid_extraction labeling feature_extraction Protocol Term Source REF Protocol Term Accession Number Experimental Factor Name CELL LINE Experimental Factor Type cell line Experimental Factor Term Source REF Experimental Factor Term Accession Number Publication Title Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. Publication Author List Celià-Terrassa T, Meca-Cortés O, Mateo F, de Paz AM, Rubio N, Arnal-Estapé A, Ell BJ, Bermudo R, Díaz A, Guerra-Rebollo M, Lozano JJ, Estarás C, Ulloa C, Álvarez-Simón D, Milà J, Vilella R, Paciucci R, Martínez-Balbás M, de Herreros AG, Gomis RR, Kang Y, Blanco J, Fernández PL, Thomson TM PubMed ID 22505459 Publication DOI 10.1172/JCI59218 Publication Status Publication Status Term Source REF Publication Status Term Accession Number Comment[SecondaryAccession] GSE24868 Comment[GEOLastUpdateDate] 2012-07-24 Comment[AEExperimentType] transcription profiling by array Comment[GEOReleaseDate] 2012-07-22 Comment[ArrayExpressSubmissionDate] 2010-10-20 SDRF File E-GEOD-24868.sdrf.txt