The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness.
The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness.
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DOI：
10.18632/oncotarget.15471
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发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Bonni S
中科院分区：
文献类型：
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作者：
Chandhoke AS;Chanda A;Karve K;Deng L;Bonni S
肿瘤转移严重降低了乳腺癌患者的生存率，但乳腺癌侵袭和转移的机制尚不完全清楚。在这里，我们报告了E3泛素连接酶Smurf 2以sumoylation依赖的方式抑制MDA-MB-231人乳腺癌细胞衍生的类器官的侵袭行为。我们还发现SUMO E3连接酶PIAS 3抑制乳腺癌细胞衍生的类器官的侵袭性生长。在机制研究中，PIAS 3通过Smurf 2的sumoylation使乳腺癌类器官保持在非侵入性状态。重要的是，E3泛素连接酶活性是sumoylated Smurf 2抑制乳腺癌细胞衍生的类器官的侵袭性生长所必需的。总的来说，我们的研究结果定义了PIAS 3-Smurf 2类小泛素化途径在抑制乳腺癌细胞侵袭性中的新作用。这些发现为开发乳腺癌的新型生物标志物和靶向治疗方法奠定了基础。
Tumor metastasis profoundly reduces the survival of breast cancer patients, but the mechanisms underlying breast cancer invasiveness and metastasis are incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts in a sumoylation-dependent manner to suppress the invasive behavior of MDA-MB-231 human breast cancer cell-derived organoids. We also find that the SUMO E3 ligase PIAS3 inhibits the invasive growth of breast cancer cell-derived organoids. In mechanistic studies, PIAS3 maintains breast cancer organoids in a non-invasive state via sumoylation of Smurf2. Importantly, the E3 ubiquitin ligase activity is required for sumoylated Smurf2 to suppress the invasive growth of breast cancer-cell derived organoids. Collectively, our findings define a novel role for the PIAS3-Smurf2 sumoylation pathway in the suppression of breast cancer cell invasiveness. These findings lay the foundation for the development of novel biomarkers and targeted therapeutic approaches in breast cancer.