WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4.
WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4.
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DOI：
10.1002/cam4.1837
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发表时间：
2018-11
期刊：
影响因子：
4
通讯作者：
Saibara T
中科院分区：
文献类型：
--
作者：
Taniuchi K;Furihata M;Naganuma S;Saibara T
WAVE 2是肌动蛋白细胞骨架调节蛋白WASP/WAVE家族的成员;不幸的是，对其在胰腺癌中的功能知之甚少。在这项研究中，我们报告了WAVE 2在胰腺癌细胞的运动和侵袭中的作用。人胰腺癌组织中WAVE 2的高表达与总生存率相关。WAVE 2在胰腺癌细胞系的细胞突起中积累。通过小干扰RNA下调WAVE 2的表达，可以减少胰腺癌细胞的突起，抑制胰腺癌细胞的运动性和侵袭性。WAVE 2通过与肌动蛋白细胞骨架蛋白α-辅肌动蛋白4（ACTN 4）形成复合物来促进胰腺癌细胞的运动和侵袭。通过小干扰RNA下调ACTN 4也通过减少细胞突起来抑制细胞的运动性和侵袭性。进一步的研究表明，WAVE 2/ACTN 4信号选择性地刺激p27磷酸化，从而增加细胞的运动性和侵袭性。这些结果表明WAVE 2和ACTN 4刺激p27磷酸化，并提供证据表明WAVE 2促进胰腺癌细胞的运动性和侵袭性。
WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in human pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines. Downregulation of WAVE2 by small interfering RNA decreased the cell protrusions and inhibited the motility and invasiveness of pancreatic cancer cells. WAVE2 promoted pancreatic cancer cell motility and invasion by forming a complex with the actin cytoskeletal protein alpha‐actinin 4 (ACTN4). Downregulation of ACTN4 by small interfering RNA also inhibited the motility and invasiveness of the cells through a decrease in cell protrusions. Further investigation showed that WAVE2/ACTN4 signaling selectively stimulated p27 phosphorylation and thereby increased the motility and invasiveness of the cells. These results suggest that WAVE2 and ACTN4 stimulate p27 phosphorylation and provide evidence that WAVE2 promotes the motility and invasiveness of pancreatic cancer cells.
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影响因子：
11.4
作者：
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