期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/ijms222212144
关键词
breast cancer; HER2; Twist1; IL17; gene expression
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Ministerio da Saude (MS), Institutos Nacionais de Ciencia e Tecnologia (INCT)-Cancer
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Breast cancer is a heterogeneous disease composed of multiple subtypes with different molecular characteristics and clinical outcomes. The role of Twist1 in HER2+ breast cancer beyond epithelial-mesenchymal transition (EMT) has been investigated, and findings suggest that Twist1 may play a role in IL-17 signaling pathway in HER2+ breast cancer.
Breast cancer (BC) is a heterogeneous disease composed of multiple subtypes with different molecular characteristics and clinical outcomes. The metastatic process in BC depends on the transcription factors (TFs) related to epithelial-mesenchymal transition (EMT), including the master regulator Twist1. However, its role beyond EMT in BC subtypes remains unclear. Our study aimed to investigate the role of Twist1, beyond EMT, in the molecular subtypes of BC. In patients, we observed the overexpression of TWIST1 in the HER2+ group. The silencing of TWIST1 in HER2+ BC cells resulted in the upregulation of 138 genes and the downregulation of 174 genes compared to control cells in a microarray assay. In silico analysis revealed correlations between Twist1 and important biological processes such as the Th17-mediated immune response, suggesting that Twist1 could be relevant for IL-17 signaling in HER2+ BC. IL-17 signaling was then examined, and it was shown that TWIST1 knockdown caused the downregulation of leading members of IL-17 signaling pathway. Taken together, our findings suggest that Twist1 plays a role on IL-17 signaling in HER2+ BC.
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