PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell
PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell
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PAK5-Egr1-MMP2信号控制乳腺癌细胞的迁移和侵袭
DOI：
10.1007/s13277-013-0824-x
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发表时间：
2013-10-01
期刊：
影响因子：
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通讯作者：
Zheng, Jun-Nian
中科院分区：
文献类型：
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作者：
Wang, Xiao-Xia;Cheng, Qian;Zheng, Jun-Nian
p21活化激酶（PAKs）被各种细胞外刺激激活，进而通过磷酸化特定丝氨酸/苏氨酸残基或通过蛋白-蛋白相互作用激活其他激酶。作为最近发现的B组PAK家族成员，PAK5在癌症中的作用尚不清楚。在本研究中，我们研究了PAK5对恶性表型的影响，如增殖、细胞周期、凋亡、迁移和侵袭。细胞生长试验和细胞周期分析一致表明，敲低PAK5可显著抑制乳腺癌细胞的增殖。伤口愈合试验。迁移实验和侵袭实验显示PAK5促进细胞迁移。此外，为了阐明PAK5影响细胞生长和迁移的潜在机制，我们检测了cyclin D1、p21、早期生长反应蛋白1 （Egr1）和基质金属蛋白酶2 （MMP2）的蛋白表达。我们的工作进一步揭示了PAK5-Egr1-MMP2信号通路是细胞迁移和侵袭的关键调节因子。这些结果表明PAK5可能是乳腺癌的潜在治疗靶点。
p21-activated kinases (PAKs) are activated by various extracellular stimuli and, in turn, activate other kinases by phosphorylating them at specific serine/threonine residues or through protein-protein interaction. As a recently identified member of the group B PAK family, the role of PAK5 in cancer is poorly understood. In this study, we investigated the effect of PAK5 on the malignant phenotype, such as proliferation, cell cycle, apoptosis, migration, and invasion. Cell growth assay and cell cycle analysis consistently showed that knockdown of PAK5 could significantly inhibit the proliferation of breast cancer cells. Wound healing assay. migration assay, and invasion assay showed that PAK5 promoted cell migration. Furthermore, in order to elucidate the underlying mechanism of PAK5 on cellular growth and migration, we examined the protein expressions of cyclin D1, p21, early growth response protein 1 (Egr1), and matrix metalloproteinase 2 (MMP2). Our work further reveals the PAK5-Egr1-MMP2 signaling pathway to be a critical regulator of cell migration and invasion. These results suggest that PAK5 may be a potential therapeutic target for breast cancer.