P21-activated kinase 7 (PAK7) interacts with and activates Wnt/β-catenin signaling pathway in breast cancer.
P21-activated kinase 7 (PAK7) interacts with and activates Wnt/β-catenin signaling pathway in breast cancer.
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P21 激活激酶 7 (PAK7) 与乳腺癌中的 Wnt/β-catenin 信号通路相互作用并激活
DOI：
10.7150/jca.24934
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发表时间：
2018
影响因子：
3.9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Li K;Xu X;He Y;Tian Y;Pan W;Xu L;Ma Y;Gao Y;Gao J;Qi Y;Wei L;Zhang J
背景：乳腺癌是女性发病率最高的肿瘤，严重威胁着女性的健康。乳腺癌的发生和发展与肿瘤抑制因子的失活或下调以及癌基因的激活或上调有关。然而，PAK 7参与乳腺癌发生发展的机制尚未完全清楚。研究方法：通过RT-qPCR和免疫组化分析PAK 7表达，并与乳腺癌组织芯片中的临床病理参数相关。采用CCK-8法、结肠形成法、创伤愈合法、transwell法和流式细胞术检测PAK 7对乳腺癌细胞的作用。采用Western blotting、TOP/FOP flash、免疫共沉淀和共定位等方法检测PAK 7与Wnt/β-catenin信号通路的关系。结果如下：PAK 7在乳腺癌组织中的表达明显增高，且与乳腺癌的病理分化程度和TNM分期呈正相关。PAK 7过表达可显著促进乳腺癌细胞的增殖和迁移，抑制细胞凋亡。与此相反，PAK 7基因敲低显著抑制乳腺癌细胞的增殖和迁移，并促进凋亡。此外，PAK 7还能激活乳腺癌细胞中的Wnt/β-catenin信号通路。进一步研究发现PAK 7可直接与GSK 3 β和β-catenin结合，通过磷酸化GSK 3 β调节β-catenin降解。结论：我们的研究表明，PAK 7作为一种癌基因，通过激活Wnt/β-catenin信号通路参与乳腺癌的进展，表明PAK 7作为乳腺癌治疗靶点的潜在适用性。
Background: Breast cancer is the highest incidence of tumor in women, which seriously threaten women's health. The occurrence and progression of breast cancer is linked to inactivation or downregulation of tumor suppressors, and activation or upregulation of oncogenes. However, the mechanism of PAK7 involving in the occurrence and progression of breast cancer is not yet fully understood. Methods: PAK7 expression was analyzed by RT-qPCR and immunohistochemistry and correlated with clinicopatholgical parameters in breast cancer tissue microarray. The effects of PAK7 on breast cancer cells were detected by CCK-8 assay, colon formation assay, wound healing and transwell assays, and flow cytometry. The relationship between PAK7 and Wnt/β-catenin signaling pathway was determined by western blotting, TOP/FOP flash, co-Immunoprecipitation and co-localization assays. Results: PAK7 expression was significantly increased in breast cancer tissues and positively correlated with pathological differentiation and TNM stage of breast cancer. Overexpression of PAK7 could significantly promote proliferation and migration of breast cancer cells, and inhibit apoptosis. In contrast, PAK7 knockdown significantly inhibited the proliferation and migration of breast cancer cells and promoted apoptosis. In addition, PAK7 could activate Wnt/β-catenin signaling pathway in breast cancer cells. Further study found that PAK7 could directly bind to GSK3β and β-catenin, and regulate β-catenin degradation by phosphorylating GSK3β. Conclusions: Our study demonstrated that PAK7, as an oncogene, involved in breast cancer progression by activating the Wnt/β-catenin signaling pathway, suggesting that the potential applicability of PAK7 as a target for breast cancer treatment.
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影响因子：
--
作者：
Bao Y;Li K;Guo Y;Wang Q;Li Z;Yang Y;Chen Z;Wang J;Zhao W;Zhang H;Chen J;Dong H;Shen K;Diamond AM;Yang W
通讯作者：
Yang W
影响因子：
16.6
作者：
Conde-Perez A;Gros G;Longvert C;Pedersen M;Petit V;Aktary Z;Viros A;Gesbert F;Delmas V;Rambow F;Bastian BC;Campbell AD;Colombo S;Puig I;Bellacosa A;Sansom O;Marais R;Van Kempen LC;Larue L
通讯作者：
Larue L
影响因子：
11.4
作者：
Abo, A;Qu, J;Minden, A
通讯作者：
Minden, A
DOI：
10.1073/pnas.220413597
发表时间：
2000-10-24
影响因子：
11.1
作者：
Fang, XJ;Yu, SX;Mills, GB
通讯作者：
Mills, GB
通过 RNA 干扰介导的 PAK5 沉默有效抑制人神经胶质瘤的发展。
影响因子：
9.2
作者：
Gu X;Wang C;Wang X;Ma G;Li Y;Cui L;Chen Y;Zhao B;Li K
通讯作者：
Li K