Transcriptome profile of the early stages of breast cancer tumoral spheroids

Rosario Pacheco-Marin, Jorge Melendez-Zajgla, Gonzalo Castillo-Rojas, Edna Mandujano-Tinoco, Alfredo Garcia-Venzor, Salvador Uribe-Carvajal, Alfredo Cabrera-Orefice, Carolina Gonzalez-Torres, Javier Gaytan-Cervantes, Irma B. Mitre-Aguilar, Vilma Maldonado

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to reliably mimic the initial growth of primary and metastatic cancer cells. However, cancer cell growth during the initial stages has not been fully explored using a genome-wide approach. Thus, in the present study, we investigated the transcriptome of breast cancer cells during the initial stages of tumoral growth using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses showed that a metastatic signature was enriched as several adhesion molecules were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which were further supported by an increase in cell migration. Interestingly, we also found that the cancer cells at this stage of growth exhibited a paradoxical hyperactivation of oxidative mitochondrial metabolism. In addition, we found a large number of regulated (long non coding RNA) lncRNAs, several of which were co-regulated with neighboring genes. The regulatory role of some of these lncRNAs on mRNA expression was demonstrated with gain of function assays. This is the first report of an early-stage MTS transcriptome, which not only reveals a complex expression landscape, but points toward an important contribution of long non-coding RNAs in the final phenotype of three-dimensional cellular models.

Original languageEnglish
Article number23373
JournalScientific Reports
Volume6
DOIs
StatePublished - 29 Mar 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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