C1GALT1 knockdown in MDA-MB-231cells suppresses breast cancer cell-induced osteoclatogenesis.
| Autor: | Jia-Hsuan Lin, 林佳宣 |
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| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 Breast cancer is the most diagnosed malignancy among women worldwide, and bones are a common place for breast cancer cells to metastasize. More recently, several studies have concluded the potential mechanisms of osteolytic bone metastasis in breast cancer is referred to high level of cancer cell secreted Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL), activators important for osteoclast differentiation. Mucin-type O-glycosylation is one of the most common post-translational modifications of proteins and it is associated with many important biological functions. Aberrant glycosylation of cell surface is associated with malignant transformation of breast cancer. Core 1 ß1,3 galactosyltransferase (C1GALT1) controls the biosynthesis of core 1 O-glycan structure, which is called T antigen. Cosmc is a molecular chaperone thought to be required for expression of active T-synthase, the only enzyme that galactosylates the Tn-antigen to form T antigen. In previous study, overexpression of C1GALT1 has recently been shown to be related to the malignant phenotypes of breast cancer cells. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteolytic bone resorption. TGF-β stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cell growth in bone. This study aims to determine the correlation between T-antigen and breast cancer bone metastasis. Our data show that knockdown C1GALT1 and Cosmc in MDA-MB-231 suppressed the mRNA and protein level of RANKL and M-CSF. Downexpression of C1GALT1 in breast cancer cell prevented osteoclast differentiation in vitro and increased the bone density by intra-cardic injection of breast cancer cells. These findings suggests that exposure of Tn-antigen in breast cancer cell suppress bone metastasis and prevented osteoclast differentiation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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