Oncogenic suppression of apoptosis uncovers a Rac1/JNK proliferation pathway activated by loss of Par3.
Oncogenic suppression of apoptosis uncovers a Rac1/JNK proliferation pathway activated by loss of Par3.
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作者：
上皮组织的破坏和生长控制的丧失是癌症的普遍特征，然而这些特征在癌症进展期间如何联系仍然知之甚少。细胞极性蛋白控制细胞和组织的组织结构，并正在成为癌症进展的重要介质。Par 3极性蛋白是一种分子支架，其功能是募集和空间组织信号传导因子，并且最近被鉴定为乳腺癌侵袭和转移的抑制因子。在这里，我们表明，在乳腺上皮细胞中的损失的Par 3促进细胞凋亡和致癌的Notch克服了细胞凋亡信号，揭示了一个意想不到的促增殖作用的损失的Par 3在乳腺肿瘤。在这种情况下，Par 3的缺失使Rac 1活性失调，从而激活Jun N-末端激酶（JNK）依赖性增殖和肿瘤生长。因此，我们证明了一种机制，通过这种机制，Par 3的损失促进增殖和肿瘤发生，这支持了乳腺上皮中Par 3的肿瘤抑制功能。
Disruption of epithelial organization and loss of growth control are universal features of carcinomas, yet how these features are linked during cancer progression remains poorly understood. Cell polarity proteins control cellular and tissue organization and are emerging as important mediators of cancer progression. The Par3 polarity protein is a molecular scaffold that functions to recruit and spatially organize signaling factors, and was recently identified as a suppressor of breast cancer invasion and metastasis. Here we show that loss of Par3 in mammary epithelial cells promotes apoptosis and that oncogenic Notch overcomes the apoptotic signal to reveal an unexpected pro-proliferative role for loss of Par3 in mammary tumors. In this context, loss of Par3 deregulates Rac1 activity to activate Jun N-terminal Kinase (JNK)-dependent proliferation and tumor growth. Thus, we demonstrate a mechanism by which loss of Par3 promotes proliferation and tumorigenesis, which supports a tumor suppressive function for Par3 in the mammary epithelium.
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影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
DOI：
10.1073/pnas.1216141110
发表时间：
2013-02-19
影响因子：
11.1
作者：
Kawazu, Masahito;Ueno, Toshihide;Mano, Hiroyuki
通讯作者：
Mano, Hiroyuki
影响因子：
9.2
作者：
Pegtel, D. Michiel;Ellenbroek, Saskia I. J.;Collard, John G.
通讯作者：
Collard, John G.
影响因子：
10.5
作者：
McCaffrey, Luke Martin;Macara, Ian G.
通讯作者：
Macara, Ian G.
影响因子：
64.5
作者：
Morais-de-Sá E;Mirouse V;St Johnston D
通讯作者：
St Johnston D