HMGA1 promotes metastatic processes in basal-like breast cancer regulating EMT and stemness.
HMGA1 promotes metastatic processes in basal-like breast cancer regulating EMT and stemness.
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DOI：
10.18632/oncotarget.1136
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Manfioletti G
中科院分区：
文献类型：
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作者：
Pegoraro S;Ros G;Piazza S;Sommaggio R;Ciani Y;Rosato A;Sgarra R;Del Sal G;Manfioletti G
乳腺癌是一种异质性疾病，进展到转移的关键标志。在本研究中，我们发现高迁移率族A1(HMGA1)蛋白在基底细胞样乳腺癌亚型的这一过程中起着重要作用。HMGA1基因敲除可诱导间充质向上皮细胞的转变，并显著降低茎的数量和自我更新能力。值得注意的是，基底样乳腺癌细胞系中HMGA1的缺失减少了体外迁移和侵袭以及体内转移的形成。在机制上，HMGA1激活了茎和关键的迁移相关基因，这些基因与Wnt/β-catenin、Notch和Pin1/突变的P53信号通路相连。此外，我们确定了一种特定的HMGA1基因表达特征，该特征在人类原发乳腺肿瘤的一大亚群中被激活，并与不良预后有关。综上所述，这些数据为HMGA1在获得乳腺癌侵袭性特征方面的作用提供了新的见解。
Breast cancer is a heterogeneous disease that progresses to the critical hallmark of metastasis. In the present study, we show that the High Mobility Group A1 (HMGA1) protein plays a fundamental role in this process in basal-like breast cancer subtype. HMGA1 knockdown induces the mesenchymal to epithelial transition and dramatically decreases stemness and self-renewal. Notably, HMGA1 depletion in basal-like breast cancer cell lines reduced migration and invasion in vitro and the formation of metastases in vivo. Mechanistically, HMGA1 activated stemness and key migration-associated genes which were linked to the Wnt/beta-catenin, Notch and Pin1/mutant p53 signalling pathways. Moreover, we identified a specific HMGA1 gene expression signature that was activated in a large subset of human primary breast tumours and was associated with poor prognosis. Taken together, these data provide new insights into the role of HMGA1 in the acquisition of aggressive features in breast cancer.