Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion.
Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion.
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DOI：
10.1083/jcb.200708048
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发表时间：
2008-03-10
期刊：
影响因子：
--
通讯作者：
Huttenlocher A
中科院分区：
文献类型：
--
作者：
Cortesio CL;Chan KT;Perrin BJ;Burton NO;Zhang S;Zhang ZY;Huttenlocher A
侵袭性癌细胞形成与基质降解相关的动态粘连结构，称为内陷。钙蛋白酶2是一种钙依赖的细胞内蛋白水解酶，它通过靶向特定的底物如Talin来调节黏附、周转和分解。在这里，我们描述了一种新的功能，通过调节内源性c-Src的活性，在侵袭足的形成和乳腺癌细胞的侵袭能力中发挥calain 2的作用。Calain缺失的乳腺癌细胞表现出受损的内陷形成，其形成可通过与Calain蛋白分解片段相对应的蛋白酪氨酸磷酸酶1B(PTP1B)的截短片段的表达而被拯救，这表明Calain通过PTP1B调节内翻。此外，PTP1B活性是有效的内陷形成和乳腺癌侵袭所必需的，这表明PTP1B可能通过其对内陷形成的影响来调节乳腺癌的进展。总之，我们的实验涉及一条新的信号通路，涉及Calain 2、PTP1B和Src，参与调节不定形和乳腺癌的侵袭。
Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel function for calpain 2 in the formation of invadopodia and in the invasive abilities of breast cancer cells through the modulation of endogenous c-Src activity. Calpain-deficient breast cancer cells show impaired invadopodia formation that is rescued by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B) corresponding to the calpain proteolytic fragment, which indicates that calpain modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for efficient invadopodia formation and breast cancer invasion, which suggests that PTP1B may modulate breast cancer progression through its effects on invadopodia. Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion.
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影响因子：
5.3
作者：
Chang, BY;Conroy, KB;Cartwright, CA
通讯作者：
Cartwright, CA
影响因子：
11.2
作者：
Libertini, SJ;Robinson, BS;Mudryj, M
通讯作者：
Mudryj, M
影响因子：
30.8
作者：
Julien, Sofi G.;Dube, Nadia;Tremblay, Michel L.
通讯作者：
Tremblay, Michel L.
影响因子：
4.8
作者：
Bjorge, JD;Pang, A;Fujita, DJ
通讯作者：
Fujita, DJ
影响因子：
11.2
作者：
Bentires-Alj, Mohamed;Neel, Benjamin G.
通讯作者：
Neel, Benjamin G.