Abstract
Cancer cells had been developed to be reprogrammed into embryonic stem like cells by induced pluripotent stem cells (iPSCs) technology, however, the tumor differentiation/dedifferentiation mechanisms had not yet been analyzed on a genome-wide scale. Here, we inserted the four stem cell transcription factor genes OCT4, SOX2, C-MYC and KLF4 into MCF cells (MCFs), represented a female breast cancer cell type, and obtained iPSCs (Mcfips) in about 3 weeks. By using the LC MS/MS iTRAQ technology, we analyzed the proteomic changes between MCFs and Mcfips. Of identified 4,616 proteins totally, 247 and 142 differentially expressed (DE) proteins were found in Mcfips compared with human induce pluripotent stem cells (Hips) and MCFs, respectively. 35 co-up and 10 co-down regulated proteins were recognized in DE proteins. Above DE proteins were categorized with GO functional classification annotation and KEGG metabolic pathway analysis into biological processes. In the protein interaction network, we found 37 and 39 hubs interacted with more than one protein in Mcfips comparing to Hips, in addition, 25 and 9 hubs were identified in Mcfips comparing to MCFs. Importantly, the mitochondria, ribosome and tumor suppressor proteins were found to be core regulators of tumor reprogramming, which might contribute to understand the mechanisms in relation to the occurrences and progression of a tumor. Thus, our study provided a valuable data for exploring the possibility to normalize the malignant phenotype.
Highlights
Breast cancer (BC) is the most common cancer and the second leading cause of cancer death in women [1, 2]
To address whether human BC cells could be reprogrammed into induced pluripotent stem cells (iPSCs), MCF cells (MCFs) were transfected by ecotropic retrovirus with four reprogramming factors, OCT3/4, SOX2, KLF4, and c-MYC at day 0
Immunofluorescence analysis showed that these Mcfips expressed TRA-1-81 and NANOG, suggesting that Mcfips were indistinguishable from the ESlike cells (Supplementary Figure 1B)
Summary
Breast cancer (BC) is the most common cancer and the second leading cause of cancer death in women [1, 2]. Since limited understanding of occurrence and development, there was no effective treatment for breast cancer besides operation. In 2006, Takahashi and Yamanaka successfully reprogrammed somatic cells to induced pluripotent stem cells (iPSCs), which brought new opportunities for pathogenetic mechanism studies and specific therapy for tumor [3]. Since somatic cells could be completely reversed into iPSCs, in theory, the tumor cells could be reprogrammed. Some results demonstrated the induced cells were iPSCs, which were distinct from natural cancer cells with regard to their sensitivity to differentiation-inducing treatment [6,7,8]. The transformation mechanism between stem cells and tumor cells was not clear. Finding the expression patterns of genes could be beneficial for study of the transformation between cancer and stem cell
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