IPO5 promotes the proliferation and tumourigenicity of colorectal cancer cells by mediating RASAL2 nuclear transportation

Wenjuan Zhang,Yanxia Lu,Jianming Zhang,Weihao Lin,Xiaomin Li,Wei Zhang,Xuenong Li,Lin Zheng

doi:10.1186/s13046-019-1290-0

Wenjuan Zhang, Yanxia Lu + Show 6 more

Open Access

https://doi.org/10.1186/s13046-019-1290-0

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Abstract

BackgroundKaryopherin nuclear transport receptors play important roles in tumour development and drug resistance and have been reported as potential biomarkers and therapeutic targets for tumour treatment. However, IPO5, one of the karyopherin nuclear transport receptor family members, remains largely uncharacterized in tumour progression.MethodsThe TCGA data, quantitative reverse transcription-PCR (qRT-PCR), western blotting, and IHC analyses were used to detect IPO5 expression in CRC tissues. A series of in vivo and in vitro experiments was utilized to demonstrate the function of IPO5 in CRC tissues. Mass spectrometry (MS), CO-IP technology, subcellular fractionation, and immunofluorescence were utilized to investigate the possible mechanisms of CRC.ResultsIPO5 was highly expressed and positively correlated with the clinicopathological characteristics of colorectal cancer tissues. Functional experiments indicated that IPO5 could promote the development of CRC. Mechanistically, we screened RASAL2, one cargo of IPO5, and further confirmed that IPO5 bound to the NLS sequence of RASAL2, mediating RASAL2 nuclear translocation and inducing RAS signal activation, thereby promoting the progression of CRC.ConclusionsTogether, our results indicate that IPO5 is overexpressed in colorectal cancer cells. By transporting RASAL2, IPO5 may play a crucial role in CRC.

Highlights

Karyopherin nuclear transport receptors play important roles in tumour development and drug resistance and have been reported as potential biomarkers and therapeutic targets for tumour treatment
By evaluating the expression levels of Importin 5 (IPO5) in eight colorectal cancer cell lines, LOVO, FHC, CACO2, RKO, SW620, SW480, HT29 and HCT116, we found that compared with that in the normal epithelial cell line FHC, IPO5 is highly expressed in cancer cells, and the highest expression levels were found in SW620, a cell line with high metastatic potential (Fig. 1d)
The immunohistochemistry results showed that IPO5 is located predominantly in the cytoplasm and the positive staining of IPO5 was significantly higher in the cancer tissues than it was in the corresponding normal tissues (Fig. 1f )

Summary

Introduction

Karyopherin nuclear transport receptors play important roles in tumour development and drug resistance and have been reported as potential biomarkers and therapeutic targets for tumour treatment. IPO5, one of the karyopherin nuclear transport receptor family members, remains largely uncharacterized in tumour progression. A large number of studies have been performed on CRC, the concrete molecular mechanisms of the formation and metastasis of CRC has not been completely clear until recently. Zhang et al Journal of Experimental & Clinical Cancer Research (2019) 38:296 our previous research, we analysed the CRC gene expression profile data of GSE41258 and sifted out a number of differentially expressed genes in which the expression of IPO5 was continuously increasing with the increasing severity from normal tissues to stage I, stage II, stage III, stage IV, and liver metastasis tumours (Additional file 1: Figure S1A) [12]. We hypothesized that IPO5 may play a key role in the development of CRC

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Conclusion