Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.
Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.
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DOI：
10.1038/emm.2017.248
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发表时间：
2018-01-26
影响因子：
12.8
通讯作者：
Lee HY
中科院分区：
文献类型：
--
作者：
Jeong BY;Cho KH;Jeong KJ;Park YY;Kim JM;Rha SY;Park CG;Mills GB;Cheong JH;Lee HY
小GTP结合蛋白Rab 25与肿瘤的形成和进展有关。然而，最近的研究表明Rab 25对癌细胞进展的影响取决于细胞谱系。在本研究中，我们阐明Rab 25诱导细胞侵袭的潜在机制。我们证明Rab 25增加β1整合素水平和随后的EGFR活化和VEGF-A表达上调，导致Snail表达增加，上皮向间质转化和癌细胞侵袭。引人注目的是，我们确定，蜗牛介导Rab 25诱导的癌细胞侵袭，通过成束蛋白表达和异位表达Rab 25的卵巢癌细胞转移到肺。因此，我们证明了β1整联蛋白/EGFR/VEGF-A/Snail信号级联通过诱导成束蛋白表达在Rab 25诱导的癌细胞侵袭性中的新作用，从而为Rab 25表达的癌细胞提供了新的生物标志物和潜在的治疗靶点。
The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.
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影响因子：
9.3
作者：
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通讯作者：
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影响因子：
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作者：
Dozynkiewicz, Marta A.;Jamieson, Nigel B.;MacPherson, Iain;Grindlay, Joan;van den Berghe, Peter V. E.;von Thun, Anne;Morton, Jennifer P.;Gourley, Charlie;Timpson, Paul;Nixon, Colin;McKay, Colin J.;Carter, Ross;Strachan, David;Anderson, Kurt;Sansom, Owen J.;Caswell, Patrick T.;Norman, Jim C.
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作者：
Kuwada, SK;Li, XF
通讯作者：
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82.9
作者：
Cheng, KW;Lahad, JP;Mills, GB
通讯作者：
Mills, GB
Snail 是胃癌进展和患者生存的独立预后预测因子
影响因子：
5.7
作者：
He, Hongyong;Chen, Weidong;Sun, Yihong
通讯作者：
Sun, Yihong