The involvement of insulin-like growth factor 2 binding protein 3 (IMP3) in pancreatic cancer cell migration, invasion, and adhesion.

Clarissa C Pasiliao,David Schaeffer,Brent W Sutherland,Sylvia S W Ng,Donald T Yapp,Che-Wei A Chang,Shannon M Valdez

doi:10.1186/s12885-015-1251-8

Abstract

BackgroundOver-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.MethodsUsing 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.ResultsKnockdown 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.ConclusionsThese results suggest that IMP3 facilitates PDAC progression by enhancing the pro-metastatic behaviour of tumour cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1251-8) contains supplementary material, which is available to authorized users.

Highlights

Over-expression of insulin-like growth factor 2 mRNA binding protein 3 (IMP3) is correlated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC)
IMP3 knockdown decreases motility, invasion, and matrix adhesion To examine the influence of IMP3 on cellular behaviour, the levels of IMP3 in pancreatic cancer cell lines were depleted with RNA interference
Depletion of IMP3 led to a significant decrease in the motility of Hs766T, a PDAC cell line derived from a lymphatic metastasis (Figure 2A)

Summary

Introduction

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. The role of this oncofetal protein in PDAC progression remained unclear. The poor prognosis of PDAC has been attributed to advanced disease at presentation, limited impact of conventional chemotherapies on disease progression, and subsequent metastatic spread and disease recurrence [2,3]. Insulin-like growth factor-2 (IGF-2) mRNA binding protein 3 (IMP3) is an oncofetal protein that may be Binding of IMP3 to mRNA transcripts exerts posttranscriptional control that influences key cellular functions involved in cancer progression. We hypothesize that IMP3 may be playing a similar role in PDAC

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