Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14.
Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14.
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Osterix 通过上调 GALNT14 降低乳腺癌细胞的化疗敏感性。
DOI：
10.1159/000485400
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发表时间：
2017
影响因子：
--
通讯作者：
Ma Changyan
中科院分区：
文献类型：
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作者：
Wu Jiahui;Chen Xiang;Bao Qianyi;Duan Rui;Jin Yucui;Shui Yifang;Yao Bing;Lu Xiangdong;Wang Yue;Cui Hongyan;Li Lingyun;Yuan Hongyan;Ma Changyan
背景/目标：Osterix（Osx）是成骨细胞分化和骨形成的关键调节因子，最近有报道称其与乳腺癌的进展有关。然而，Osx在乳腺癌中的确切作用仍不清楚。方法：采用MTT法测定肿瘤细胞对化疗药物的敏感性。通过高通量Illumina测序获得靶基因，并在体外和体内进行确认。Hoechst染色和蛋白质印迹分析细胞凋亡。包括129个来自乳腺癌患者的样品的组织微阵列用于免疫组织化学（IHC）测定。结果如下：Osx的过表达降低了乳腺癌细胞的化疗敏感性，而Osx的敲低增加了乳腺癌细胞的化疗敏感性。特别是，我们发现，降低化疗敏感性的效果是显着相关的多肽N-乙酰氨基半乳糖转移酶14（GALNT 14）的表达升高。Osx过表达细胞中GALNT 14的沉默恢复了降低的化疗敏感性。相反，GALNT 14在Osx敲除细胞中的过表达废除了乳腺癌细胞中增加的化学敏感性。此外，我们发现Osx通过增强抗凋亡作用降低GALNT 14依赖的化疗敏感性。GALNT 14表达与乳腺癌分期以及无病生存率（DFS）显著相关。结论：Osx在乳腺癌的化疗敏感性中起重要作用，抑制Osx表达可能是提高乳腺癌化疗敏感性的一种治疗策略。
Background/Aims: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. Methods: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. Results: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. Conclusion: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.