IGFBP-rP1 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer.

S Zhu,J Zhang,F Xu,Y Ma,M Lai,E Xu,W Ruan,Q Huang

doi:10.1038/cddis.2015.59

Abstract

Epithelial–mesenchymal transition (EMT) was initially recognized during organogenesis and has recently been reported to be involved in promoting cancer invasion and metastasis. Cooperation of transforming growth factor-β (TGF-β) and other signaling pathways, such as Ras and Wnt, is essential to inducing EMT, but the molecular mechanisms remain to be fully determined. Here, we reported that insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), a potential tumor suppressor, controls EMT in colorectal cancer progression. We revealed the inhibitory role of IGFBP-rP1 through analyses of clinical colorectal cancer samples and various EMT and metastasis models in vitro and in vivo. Moreover, we demonstrated that IGFBP-rP1 suppresses EMT and tumor metastasis by repressing TGF-β-mediated EMT through the Smad signaling cascade. These data establish that IGFBP-rP1 functions as a suppressor of EMT and metastasis in colorectal cancer.

Highlights

More than 90% of these deaths are attributed to local invasion and distant metastasis.[2]
Considering the proposed correlation between IGFBP-rP1 and clinical outcome, we extended our analysis to the relationship between IGFBP-rP1 expression and clinicopathological parameters
Inhibition of epithelial–mesenchymal transition (EMT) and metastasis by IGFBP-rP1 S Zhu et al tissue is correlated with a favorable prognosis.[20]

Summary

Introduction

More than 90% of these deaths are attributed to local invasion and distant metastasis.[2]. A variety of extracellular signals can trigger EMT, and transforming growth factor β (TGF-β) is considered to be a potent inducer of EMT in an autocrine or paracrine manner.[11] It is known that TGF-β has dual roles during tumor progression It inhibits tumor growth in the early phase, but paradoxically, in the late phase it acts as a tumor promoter by enhancing EMT and promoting tumor cell invasion in primary carcinomas.[12,13] TGF-β binds to its receptors and activates Smad[2] and Smad[3], phosphorylated SMAD2/3 partner with Smad[4] to translocate into the nucleus where SMAD complexes control target gene transcription, including EMT- and motility-related genes.[14]. IGFBP-rP1 has been confirmed as a master regulator of cancer-cell fate, its functional role in EMT and metastasis remains largely unknown

Methods

Results

Conclusion