Decorin-mediated suppression of tumorigenesis, invasion, and metastasis in inflammatory breast cancer.
Decorin-mediated suppression of tumorigenesis, invasion, and metastasis in inflammatory breast cancer.
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DOI：
10.1038/s42003-020-01590-0
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发表时间：
2021-01-15
影响因子：
5.9
通讯作者：
Debeb BG
中科院分区：
文献类型：
--
作者：
Hu X;Villodre ES;Larson R;Rahal OM;Wang X;Gong Y;Song J;Krishnamurthy S;Ueno NT;Tripathy D;Woodward WA;Debeb BG
炎性乳腺癌 (IBC) 是一种临床上独特且高度侵袭性的乳腺癌，发病迅速且极易转移。 IBC 侵袭性和转移倾向的分子机制在很大程度上尚不清楚。在此，我们报告核心蛋白聚糖 (DCN) 是一种富含亮氨酸的细胞外基质蛋白多糖，在 IBC 患者的肿瘤中表达下调。 IBC 细胞中 DCN 的过表达可显着降低体外迁移、侵袭和癌症干细胞，并抑制 IBC 异种移植小鼠模型中的肿瘤生长和转移。从机制上讲，DCN 通过破坏 E-钙粘蛋白的稳定性并抑制 EGFR/ERK 信号传导来抑制 IBC 中的侵袭和肿瘤生长。 DCN 物理结合 IBC 细胞中的 E-钙粘蛋白，并通过自噬相关的溶酶体途径加速其降解。我们确定 DCN 通过负向调节 E-cadherin/EGFR/ERK 轴来抑制 IBC 细胞的肿瘤发生和转移。我们的研究结果为 IBC 提供了一种潜在的治疗策略，并为 IBC 病理学提供了一种新的机制。胡晓丁等人。发现与正常乳腺组织和一些其他类型的乳腺癌相比，炎性乳腺癌患者中蛋白聚糖核心蛋白的表达降低。他们证明，核心蛋白聚糖通过破坏 E-钙粘蛋白-EGFR 信号轴的稳定性，在癌细胞和人类异种移植小鼠模型中发挥肿瘤抑制作用，他们的发现表明了这种侵袭性乳腺癌的潜在治疗策略。
Inflammatory breast cancer (IBC) is a clinically distinct and highly aggressive form of breast cancer with rapid onset and a strong propensity to metastasize. The molecular mechanisms underlying the aggressiveness and metastatic propensity of IBC are largely unknown. Herein, we report that decorin (DCN), a small leucine-rich extracellular matrix proteoglycan, is downregulated in tumors from patients with IBC. Overexpression of DCN in IBC cells markedly decreased migration, invasion, and cancer stem cells in vitro and inhibited tumor growth and metastasis in IBC xenograft mouse models. Mechanistically, DCN functioned as a suppressor of invasion and tumor growth in IBC by destabilizing E-cadherin and inhibiting EGFR/ERK signaling. DCN physically binds E-cadherin in IBC cells and accelerates its degradation through an autophagy-linked lysosomal pathway. We established that DCN inhibits tumorigenesis and metastasis in IBC cells by negatively regulating the E-cadherin/EGFR/ERK axis. Our findings offer a potential therapeutic strategy for IBC, and provide a novel mechanism for IBC pathobiology. Xiaoding Hu et al. find that expression of the proteoglycan decorin is decreased in patients with inflammatory breast cancer compared to normal breast tissue and some other types of breast cancer. They demonstrate that decorin acts as a tumor suppressor in cancer cells and human xenograft mouse models by destabilizing the E-cadherin-EGFR signaling axis, and their findings suggest potential therapeutic strategies for this aggressive breast cancer.
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DOI：
10.1002/stem.1219
发表时间：
2012-11
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Debeb BG;Lacerda L;Xu W;Larson R;Solley T;Atkinson R;Sulman EP;Ueno NT;Krishnamurthy S;Reuben JM;Buchholz TA;Woodward WA
通讯作者：
Woodward WA
影响因子：
6.9
作者：
Goyal, Atul;Neill, Thomas;Owens, Rick T.;Schaefer, Liliana;Iozzo, Renato V.
通讯作者：
Iozzo, Renato V.
影响因子：
6.2
作者：
Douglas, Timothy;Heinemann, Sascha;Worch, Hartmut
通讯作者：
Worch, Hartmut
影响因子：
4.8
作者：
Iozzo, RV;Moscatello, DK;Eichstetter, I
通讯作者：
Eichstetter, I
CCDC178通过调节失巢凋亡促进肝细胞癌转移
影响因子：
8
作者：
Hu, X.;Zhao, Y.;Wu, J.
通讯作者：
Wu, J.