The involvement of insulin-like growth factor 2 binding protein 3 (IMP3) in pancreatic cancer cell migration, invasion, and adhesion.
The involvement of insulin-like growth factor 2 binding protein 3 (IMP3) in pancreatic cancer cell migration, invasion, and adhesion.
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DOI：
10.1186/s12885-015-1251-8
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发表时间：
2015-04-11
期刊：
影响因子：
3.8
通讯作者：
Ng SS
中科院分区：
文献类型：
--
作者：
Pasiliao CC;Chang CW;Sutherland BW;Valdez SM;Schaeffer D;Yapp DT;Ng SS
胰岛素样生长因子2 mRNA结合蛋白3（IMP3）的过度表达与胰腺导管腺癌（PDAC）的不良预后相关。先前研究其他癌症类型的研究表明，IMP3参与了肿瘤细胞特有的几种细胞功能的调节。然而，这种癌胚蛋白在PDAC进展中的作用仍不清楚。使用siRNA，我们检测了IMP3抑制对PDAC细胞的运动性、侵袭能力和基质粘附的影响。此外，我们还评估了IMP耗竭后细胞因子相关基因的表达。IMP3的敲低显著降低了体外选择的PDAC细胞的运动性、侵袭性和细胞外基质粘附。此外，IMP 3耗尽的细胞表现出较低水平的CD 44蛋白和KIF 11 mRNA。此外，我们还观察到IMP3敲低后下游RhoA信号传导减少，表明IMP3调节参与细胞骨架组织的蛋白质水平。这些结果表明，IMP 3通过增强肿瘤细胞的促转移行为促进PDAC进展。本文的在线版本（doi：10.1186/s12885-015-1251-8）包含补充材料，可供授权用户使用。
Over-expression of insulin-like growth factor 2 mRNA binding protein 3 (IMP3) is correlated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Previous studies examining other cancer types have implicated IMP3 in the regulation of several cellular functions that are characteristic of tumour cells. However, the role of this oncofetal protein in PDAC progression remained unclear. Using siRNA, we examined the effect of IMP3 inhibition on the motility, invasive ability, and matrix adhesion of PDAC cells. In addition, we also evaluated the expression of cytoskeleton-associated genes following IMP depletion. Knockdown of IMP3 significantly decreased the motility, invasion, and extracellular matrix adhesion of select PDAC cells in vitro. In addition, IMP3-depleted cells exhibited lower levels of CD44 protein and KIF11 mRNA. Moreover, we also observed a reduction in downstream RhoA signaling following IMP3 knockdown, indicating that IMP3 modulates the levels of proteins involved in cytoskeletal organization. These results suggest that IMP3 facilitates PDAC progression by enhancing the pro-metastatic behaviour of tumour cells. The online version of this article (doi:10.1186/s12885-015-1251-8) contains supplementary material, which is available to authorized users.