Rb suppresses collective invasion, circulation and metastasis of breast cancer cells in CD44-dependent manner.
Rb suppresses collective invasion, circulation and metastasis of breast cancer cells in CD44-dependent manner.
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DOI：
10.1371/journal.pone.0080590
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Godar S
中科院分区：
文献类型：
--
作者：
Kim KJ;Godarova A;Seedle K;Kim MH;Ince TA;Wells SI;Driscoll JJ;Godar S
基底细胞样乳腺癌（BLC）表现为肿瘤外淋巴管浸润，具有高度转移性，可能是通过血行途径转移，具有增强的CD44癌蛋白表达和相对低水平的视网膜母细胞瘤（Rb）肿瘤抑制因子。然而，这些特征之间的因果关系尚不清楚。在这里，我们表明，Rb作为一个关键的抑制多阶段的转移进展。首先，Rb在体外抑制集体细胞迁移（CCM）和CD44依赖的F-actin阳性突起的形成，在体内抑制基于细胞簇的淋巴血管侵袭。其次，Rb抑制单个癌细胞和细胞簇释放到血源性循环中以及随后在肺部的转移性生长。最后，CD44表达是集体运动和Rb功能丧失引发的转移进展的所有后续阶段所必需的。总之，我们的研究结果表明Rb/CD44通路是CCM和BLC转移进展的重要调节因子，并且是抗BLC治疗的有希望的靶点。
Basal-like breast carcinomas (BLCs) present with extratumoral lymphovascular invasion, are highly metastatic, presumably through a hematogenous route, have augmented expression of CD44 oncoprotein and relatively low levels of retinoblastoma (Rb) tumor suppressor. However, the causal relation among these features is not clear. Here, we show that Rb acts as a key suppressor of multiple stages of metastatic progression. Firstly, Rb suppresses collective cell migration (CCM) and CD44-dependent formation of F-actin positive protrusions in vitro and cell-cluster based lymphovascular invasion in vivo. Secondly, Rb inhibits the release of single cancer cells and cell clusters into the hematogenous circulation and subsequent metastatic growth in lungs. Finally, CD44 expression is required for collective motility and all subsequent stages of metastatic progression initiated by loss of Rb function. Altogether, our results suggest that Rb/CD44 pathway is a crucial regulator of CCM and metastatic progression of BLCs and a promising target for anti-BLCs therapy.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
11.2
作者：
Onder, Tamer T.;Gupta, Piyush B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
DOI：
10.1186/bcr3217
发表时间：
2012-07-02
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Matise LA;Palmer TD;Ashby WJ;Nashabi A;Chytil A;Aakre M;Pickup MW;Gorska AE;Zijlstra A;Moses HL
通讯作者：
Moses HL
影响因子：
64.5
作者：
Godar S;Ince TA;Bell GW;Feldser D;Donaher JL;Bergh J;Liu A;Miu K;Watnick RS;Reinhardt F;McAllister SS;Jacks T;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
15.9
作者：
Brown, Rhonda L.;Reinke, Lauren M.;Cheng, Chonghui
通讯作者：
Cheng, Chonghui