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首页> 外文期刊>Cellular Signalling >STAT3 interacts with Skp2/p27/p21 pathway to regulate the motility and invasion of gastric cancer cells
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STAT3 interacts with Skp2/p27/p21 pathway to regulate the motility and invasion of gastric cancer cells

机译：STAT3与Skp2 / p27 / p21途径相互作用以调节胃癌细胞的活力和侵袭

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The interleukin-6 (IL-6)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway mediates cell proliferation and migration. S-phase kinase-associated protein-2 (Skp2) catalyzes the ubiquitylation of p27 and p21. Here we investigated that the cross-talk of the two pathways regulates motility and invasion of gastric cancer SGC7901 and MGC803 cells. Both cell lines endogenously secret IL-6, and blockage of IL-6 or JAK2 inhibited the activation of JAK2 and STAT3. Depletion of STAT3 downregulated Skp2 expression, and thereby increased the expression of p27 and p21. The depletion of STAT3 inhibited the ability of cells to migrate and invade, and impaired the cellular cytoskeleton mainly microtubules; while the depletion of p27 partially restored the impaired ability to migrate, and reversed the impaired microfilaments, further inhibited the ability to invade, but had little effect on microtubules and cellular adhering ability of STAT3-depleted cells. STAT3 depletion inhibited the activity of RhoA and the interaction with stathmin, downregulated the expression of pFAK (phosphorylated focal adhesion kinase), acetylated-tubulin, RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and Sp1, upregulated E-cadherin, and reduced the activities of MMP (matrix metalloproteinase)-2 and -9. The depletion of p27 increased RhoA (Ras homolog family member A) activity, upregulated RECK, and downregulated E-cadherin and Sp1 in STAT3-depleted cells. The results indicate that the interaction between STAT3 and Skp2/p27/p21 pathway plays an important role in mediating the motility, migration and invasion of gastric cancer cells, and inhibition of STAT3 may be a useful therapeutic approach for metastasis of gastric cancer, but caution needs to be taken for its effects on Skp2/p27/p21 pathway.
机译：白介素6（IL-6）/ Janus激酶2（JAK2）/信号转导子和转录激活子3（STAT3）通路介导细胞增殖和迁移。 S期激酶相关蛋白2（Skp2）催化p27和p21的泛素化。在这里，我们研究了这两种途径的相互作用调节胃癌SGC7901和MGC803细胞的运动性和侵袭性。两种细胞系均内源性分泌IL-6，IL-6或JAK2的阻滞抑制了JAK2和STAT3的激活。 STAT3的耗尽下调Skp2表达，从而增加p27和p21的表达。 STAT3的消耗抑制了细胞迁移和侵袭的能力，并损害了细胞骨架，主要是微管。而p27的耗竭可部分恢复受损的迁移能力，并逆转受损的微丝，进一步抑制其侵袭能力，但对STAT3耗竭细胞的微管和细胞粘附能力影响不大。 STAT3耗竭抑制RhoA的活性以及与Stathmin的相互作用，下调pFAK（磷酸化的黏着斑激酶），乙酰化的微管蛋白，RECK（具有kazal图案的诱导半胱氨酸的还原蛋白）和Sp1的表达，上调E-钙粘蛋白，并降低了MMP（基质金属蛋白酶）-2和-9的活性。 p27的耗尽增加了STAT3缺失细胞中RhoA（Ras同源家族A成员）的活性，上调了RECK，并下调了E-钙粘蛋白和Sp1。结果表明，STAT3和Skp2 / p27 / p21通路之间的相互作用在介导胃癌细胞的运动，迁移和侵袭中起着重要作用，抑制STAT3可能是治疗胃癌转移的有效方法，但要注意需要考虑其对Skp2 / p27 / p21途径的影响。

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