TY - JOUR
T1 - Transcriptome profile of the early stages of breast cancer tumoral spheroids
AU - Pacheco-Marin, Rosario
AU - Melendez-Zajgla, Jorge
AU - Castillo-Rojas, Gonzalo
AU - Mandujano-Tinoco, Edna
AU - Garcia-Venzor, Alfredo
AU - Uribe-Carvajal, Salvador
AU - Cabrera-Orefice, Alfredo
AU - Gonzalez-Torres, Carolina
AU - Gaytan-Cervantes, Javier
AU - Mitre-Aguilar, Irma B.
AU - Maldonado, Vilma
N1 - Funding Information:
Pacheco-Marin Rosario was supported by a fellowship from CONACYT (CVU 225990), and this study is part of her doctoral thesis from the posgrade in Biologicas Sciences Doctorate Program, Faculty of Medicine, UNAM. Thanks to the training and support during her PhD. Julio Perez Carreon (Institute of Genomic Medicine) and Alejandro López Saavedra (Nacional Cancer Institute of Mexico) to facilitate the use of microscopes and photographs of MTS, Alfredo Mendoza Vargas and his staff for RNA sequencing and Valeria Jurado Quintanar for histological preparation of MTS (High Technology Units, National Institute of Genomic Medicine, Mexico) and Jose Luis Cruz Colin for their support in cell culture (National Institute of Genomic Medicine, Mexico).
PY - 2016/3/29
Y1 - 2016/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84962374503&partnerID=8YFLogxK
U2 - 10.1038/srep23373
DO - 10.1038/srep23373
M3 - Article
C2 - 27021602
AN - SCOPUS:84962374503
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 23373
ER -