PRL-3 promotes the motility, invasion, and metastasis of LoVo colon cancer cells through PRL-3-integrin beta1-ERK1/2 and-MMP2 signaling.
PRL-3 promotes the motility, invasion, and metastasis of LoVo colon cancer cells through PRL-3-integrin beta1-ERK1/2 and-MMP2 signaling.
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PRL-3 通过 PRL-3-整合素 beta1-ERK1/2 和-MMP2 信号传导促进 LoVo 结肠癌细胞的运动、侵袭和转移。
DOI：
10.1186/1476-4598-8-110
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发表时间：
2009-11-24
期刊：
影响因子：
37.3
通讯作者：
Shou C
中科院分区：
文献类型：
--
作者：
Peng L;Xing X;Li W;Qu L;Meng L;Lian S;Jiang B;Wu J;Shou C
再生肝磷酸酶-3（PRL-3）在肿瘤转移中起重要作用，但其机制尚不清楚。我们在前期的研究中观察到PRL-3可以降低HEK 293细胞整合素β1的酪氨酸磷酸化水平，增强ERK 1/2的激活。本研究旨在探讨PRL-3与整合素β1信号通路的关系及其在结肠癌细胞LoVo运动、侵袭和转移中的作用。采用Transwell小室法和裸鼠模型分别观察LoVo结肠癌细胞的运动、侵袭和凋亡情况。Western blot和RT-PCR检测siRNA和慢病毒对整合素β1的抑制作用。通过Western blot、免疫荧光、免疫共沉淀和酶谱分析检测PRL-3对整合素β1、ERK 1/2和介导运动、侵袭和转移的MMPs的影响。我们发现PRL-3与整合素β1相关，其表达与ERK 1/2磷酸化在结肠癌组织中呈正相关。siRNA去除整合素β1后，不仅能抑制PRL-3对ERK 1/2的激活，而且能抑制PRL-3诱导的LoVo细胞运动和侵袭。类似地，用U 0126抑制ERK 1/2磷酸化或用GM 6001抑制MMP活性也损害PRL-3诱导的侵袭。此外，PRL-3促进MMP 2的明胶分解活性，并且这种刺激与TIMP 2表达降低相关。此外，当用shRNA干扰整合素β1表达时，PRL-3刺激的LoVo细胞在裸鼠模型中的肺转移被抑制。我们的研究结果表明，PRL-3在结肠癌的运动，侵袭和转移中的作用是由整合素β1-ERK 1/2-MMP 2信号转导关键控制的。
Phosphatase of regenerating liver-3 (PRL-3) plays a causative role in tumor metastasis, but the underlying mechanisms are not well understood. In our previous study, we observed that PRL-3 could decrease tyrosine phosphorylation of integrin β1 and enhance activation of ERK1/2 in HEK293 cells. Herein we aim to explore the association of PRL-3 with integrin β1 signaling and its functional implications in motility, invasion, and metastasis of colon cancer cell LoVo. Transwell chamber assay and nude mouse model were used to study motility and invasion, and metastsis of LoVo colon cancer cells, respectively. Knockdown of integrin β1 by siRNA or lentivirus were detected with Western blot and RT-PCR. The effect of PRL-3 on integrin β1, ERK1/2, and MMPs that mediate motility, invasion, and metastasis were measured by Western blot, immunofluorencence, co-immunoprecipitation and zymographic assays. We demonstrated that PRL-3 associated with integrin β1 and its expression was positively correlated with ERK1/2 phosphorylation in colon cancer tissues. Depletion of integrin β1 with siRNA, not only abrogated the activation of ERK1/2 stimulated by PRL-3, but also abolished PRL-3-induced motility and invasion of LoVo cells in vitro. Similarly, inhibition of ERK1/2 phosphorylation with U0126 or MMP activity with GM6001 also impaired PRL-3-induced invasion. In addition, PRL-3 promoted gelatinolytic activity of MMP2, and this stimulation correlated with decreased TIMP2 expression. Moreover, PRL-3-stimulated lung metastasis of LoVo cells in a nude mouse model was inhibited when integrin β1 expression was interfered with shRNA. Our results suggest that PRL-3's roles in motility, invasion, and metastasis in colon cancer are critically controlled by the integrin β1-ERK1/2-MMP2 signaling.
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DOI：
10.1111/j.1749-6632.1999.tb07675.x
发表时间：
1999-01-01
期刊：
INHIBITION OF MATRIX METALLOPROTEINASES: THERAPEUTIC APPLICATIONS
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1016/j.bbrc.2006.07.043
发表时间：
2006-09-15
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
7.5
作者：
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