KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells.
KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells.
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DOI：
10.1016/j.neo.2014.10.007
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发表时间：
2014-12
期刊：
影响因子：
4.8
通讯作者：
Saibara, Toshiji
中科院分区：
文献类型：
--
作者：
Taniuchi, Keisuke;Furihata, Mutsuo;Saibara, Toshiji
胰腺癌是侵袭性的，因为它们是高度侵袭性和高度转移性的;此外，缺乏对侵袭性胰腺癌的有效治疗。在这里，我们报告说，运动驱动蛋白KIF 20 A促进胰腺癌细胞的运动和侵袭，通过运输RNA结合蛋白IGF 2BP 3和IGF 2BP 3结合的转录物向细胞突起沿着微管。我们先前报道了IGF 2BP 3及其靶转录物组装成胰腺癌细胞的细胞质应激颗粒，并且IGF 2BP 3通过调节细胞突起中IGF 2BP 3结合转录物的局部翻译来促进胰腺癌细胞的运动性和侵袭性。我们发现，敲低KIF 20 A抑制了细胞突起中含有IGF 2BP 3的应激颗粒的积累，并抑制了突起中特定IGF 2BP 3结合转录物ARF 6和ARHGEF 4的局部蛋白表达。我们的研究结果提供了对KIF 20 A介导的含有IGF 2BP 3的应激颗粒的运输的调节与胰腺癌的运动性和侵袭性的调节之间的联系的深入了解。
Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.
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影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
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作者：
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11.2
作者：
Taniuchi, Keisuke;Nishimori, Isao;Hollingsworth, Michael A.
通讯作者：
Hollingsworth, Michael A.