FH535 inhibited migration and growth of breast cancer cells.
FH535 inhibited migration and growth of breast cancer cells.
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DOI：
10.1371/journal.pone.0044418
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shriver CD
中科院分区：
文献类型：
--
作者：
Iida J;Dorchak J;Lehman JR;Clancy R;Luo C;Chen Y;Somiari S;Ellsworth RE;Hu H;Mural RJ;Shriver CD
有大量证据表明，WNT信号通路在包括乳腺癌在内的各种癌细胞类型中被激活。先前的研究报道，FH 535，一种WNT信号通路的小分子抑制剂，降低了癌细胞的生长，但不是正常的成纤维细胞，这表明该通路在肿瘤进展和转移中起作用。在这项研究中，我们测试了FH 535作为乳腺癌细胞恶性表型的潜在抑制剂，包括迁移，侵袭和生长。FH 535在体外显著抑制三阴性（TN）乳腺癌细胞系（MDA-MB 231和HCC 38）的生长、迁移和侵袭。我们证明，当在三维（3D）I型胶原凝胶中培养时，FH 535是TN乳腺癌细胞系（HCC 38和MDA-MB-231）的有效生长抑制剂，但对其他非TN乳腺癌细胞系（MCF-7、T47 D或SK-Br 3）不是。Western印迹分析表明，用FH 535处理MDA-MB-231细胞显著抑制NEDD 9的表达，但不激活FAK、Src或下游靶点如p38和Erk 1/2。我们证明，在MDA-MB-231细胞中，NEDD 9与CSPG 4特异性相关，但与β1整合素或CD 44无关。乳腺癌组织中基因表达谱的分析表明，CSPG 4表达在基底型乳腺癌中高于任何其他亚型，其中许多是TN。这些结果表明，不仅涉及经典的WNT信号通路的迁移和入侵的机制，但也治疗谁开发TN乳腺癌患者的新策略。
There is substantial evidence indicating that the WNT signaling pathway is activated in various cancer cell types including breast cancer. Previous studies reported that FH535, a small molecule inhibitor of the WNT signaling pathway, decreased growth of cancer cells but not normal fibroblasts, suggesting this pathway plays a role in tumor progression and metastasis. In this study, we tested FH535 as a potential inhibitor for malignant phenotypes of breast cancer cells including migration, invasion, and growth. FH535 significantly inhibited growth, migration, and invasion of triple negative (TN) breast cancer cell lines (MDA-MB231 and HCC38) in vitro. We demonstrate that FH535 was a potent growth inhibitor for TN breast cancer cell lines (HCC38 and MDA-MB-231) but not for other, non-TN breast cancer cell lines (MCF-7, T47D or SK-Br3) when cultured in three dimensional (3D) type I collagen gels. Western blotting analyses suggest that treatment of MDA-MB-231 cells with FH535 markedly inhibited the expression of NEDD9 but not activations of FAK, Src, or downstream targets such as p38 and Erk1/2. We demonstrated that NEDD9 was specifically associated with CSPG4 but not with β1 integrin or CD44 in MDA-MB-231 cells. Analyses of gene expression profiles in breast cancer tissues suggest that CSPG4 expression is higher in Basal-type breast cancers, many of which are TN, than any other subtypes. These results suggest not only a mechanism for migration and invasion involving the canonical WNT-signaling pathways but also novel strategies for treating patients who develop TN breast cancer.
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影响因子：
11.4
作者：
Bravo-Cordero, Jose J.;Marrero-Diaz, Raquel;Montoya, Maria C.
通讯作者：
Montoya, Maria C.
影响因子：
4.8
作者：
Iida, J;Pei, D;McCarthy, JB
通讯作者：
McCarthy, JB
Wnt途径基因的遗传变化是乳房化生癌中的常见事件。
DOI：
10.1158/1078-0432.ccr-07-4379
发表时间：
2008-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hayes MJ;Thomas D;Emmons A;Giordano TJ;Kleer CG
通讯作者：
Kleer CG
影响因子：
7.5
作者：
Geyer, Felipe C.;Lacroix-Triki, Magali;Reis-Filho, Jorge S.
通讯作者：
Reis-Filho, Jorge S.
影响因子：
3.3
作者：
Knutson, JR;Iida, J;McCarthy, JB
通讯作者：
McCarthy, JB