SRGN-TGFβ2 regulatory loop confers invasion and metastasis in triple-negative breast cancer.
SRGN-TGFβ2 regulatory loop confers invasion and metastasis in triple-negative breast cancer.
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SRGN-TGFβ2 调节环赋予三阴性乳腺癌侵袭和转移
DOI：
10.1038/oncsis.2017.53
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发表时间：
2017-07-10
期刊：
影响因子：
6.2
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Zhang Z;Deng Y;Zheng G;Jia X;Xiong Y;Luo K;Qiu Q;Qiu N;Yin J;Lu M;Liu H;Gu Y;He Z
三阴性乳腺癌(TNBC)患者复发或转移的风险很高，与此风险相关的分子机制尚不清楚。蛋白多糖丝氨酸(SRGN)蛋白参与肿瘤转移，但其在TNBC中的作用尚未阐明。本研究探讨sRGN基因在肿瘤细胞和组织中的表达及其对转化生长因子β-2及其下游信号转导的调节作用。我们的结果表明，SRGN在TNBC细胞系和肿瘤组织中的表达水平显著高于非TNBC细胞和组织。我们使用shRNA抑制SRGN的表达和蛋白分泌，我们观察到这在体外抑制了TNBC癌细胞的侵袭运动，并在体内抑制了TNBC癌细胞的转移。SRGN蛋白通过激活CD44CREB1信号通路增加转化生长因子β2(TGFCREB2)的表达和分泌，促进β细胞上皮向间充质转化。此外，转化生长因子β-2通过激活Smad3靶向肿瘤细胞中的SRGN相关启动子区域，增加了SRGNmRNA和蛋白的表达。我们的研究结果表明，SRGN通过自分泌和旁分泌途径与调节肿瘤转移的转化生长因子β-2相互作用。SRGN可作为TNBC药物或治疗药物开发的潜在靶点。
Patients with triple-negative breast cancers (TNBC) are at a high risk for a recurrent or metastatic disease, and the molecular mechanisms associated with this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the SRGN gene expression and how it regulates TGFβ2 and the downstream signaling of TGFβ2 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues. We inhibited SRGN expression and protein secretion using shRNA and we observed this inhibited the invasive motility of TNBC cancer cells in vitro and metastasis of TNBC cancer cells in vivo. SRGN protein treatment increased the expression and secretion of transforming growth factor-β2 (TGFβ2) by activating CD44/CREB1 signaling and promoted epithelial-to-mesenchymal transition in TNBC cells. Moreover, TGFβ2 treatment increased the mRNA and protein expression of the SRGN gene by activating Smad3 to target the SRGN relative promoter domain in TNBC cells. Our findings demonstrate that SRGN interacts with TGFβ2 which regulates TNBC metastasis via the autocrine and paracrine routes. SRGN could serve as a potential target for development of agents or therapeutics for the TNBC.
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影响因子：
64.8
作者：
Shalapour S;Font-Burgada J;Di Caro G;Zhong Z;Sanchez-Lopez E;Dhar D;Willimsky G;Ammirante M;Strasner A;Hansel DE;Jamieson C;Kane CJ;Klatte T;Birner P;Kenner L;Karin M
通讯作者：
Karin M
影响因子：
11.4
作者：
Niemann, C. U.;Kjeldsen, L.;Borregaard, N.
通讯作者：
Borregaard, N.
影响因子：
28.2
作者：
Rodon, Laura;Gonzalez-Junca, Alba;Seoane, Joan
通讯作者：
Seoane, Joan
影响因子：
5.4
作者：
Skliris, Antonis;Happonen, Kaisa E.;Theocharis, Achilleas D.
通讯作者：
Theocharis, Achilleas D.
Serglycin (SRGN) 过度表达预示肝细胞癌患者预后不良
影响因子：
3.4
作者：
He, Lu;Zhou, Xinke;Hong, Jian
通讯作者：
Hong, Jian