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International Journal of Colorectal Disease

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01-07-2013 | Original Article

SLIT2 inhibits cell migration in colorectal cancer through the AKT–GSK3β signaling pathway

Authors: Wei-Feng Chen, Wei-Dong Gao, Quan-Lin Li, Ping-Hong Zhou, Mei-Dong Xu, Li-Qing Yao

Published in: International Journal of Colorectal Disease | Issue 7/2013

Abstract

Purpose

Colorectal cancer is a common malignancy and one of the major causes of cancer-related deaths worldwide. Similar to other human cancers, tumor metastasis is the biggest obstacle in the clinical treatment of colorectal cancer. In this study, we explored the functional role of SLIT2 in colon tumor metastasis and the relevant molecular mechanisms.

Methods

Immunohistochemistry, Western blotting, and quantitative reverse transcription-polymerase chain reaction were used to measure SLIT2 expression in colorectal tumor tissues in the presence or absence of metastasis. Wound-healing assays, Transwell assays, Western blotting, and immunofluorescence assays were used to examine the effects of SLIT2 on SW480 and NCM460 cell migration and the epithelial-to-mesenchymal transition (EMT). An AKT inhibitor was introduced to examine the mechanism underlying SLIT2-mediated suppression of NCM460 cell migration.

Results

Higher SLIT2 expression was detected in metastasis-positive tumor tissues, and this upregulation was beneficial for the overall survival of patients with colorectal cancer. Either the addition of purified SLIT2 or overexpression of SLIT2 inhibited SW480 cell migration, whereas the depletion of SLIT2 with shRNA enhanced the migratory ability of NCM460 cells. Meanwhile, SLIT2 depletion also induced β-catenin accumulation and altered the expression levels of several molecules related to EMT in NCM460 cells. AKT inhibition abrogated the effects of SLIT2 depletion on EMT and migration in NCM460 cells.

Conclusions

SLIT2 suppresses colon tumor metastasis, and it exerts its suppressive activity against colorectal cancer metastasis by restraining AKT signaling and EMT, thus making it a potential clinical prognosis marker in colorectal cancer.

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Title: SLIT2 inhibits cell migration in colorectal cancer through the AKT–GSK3β signaling pathway
Authors: Wei-Feng Chen
Wei-Dong Gao
Quan-Lin Li
Ping-Hong Zhou
Mei-Dong Xu
Li-Qing Yao
Publication date: 01-07-2013
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 7/2013
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-013-1641-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SLIT2 inhibits cell migration in colorectal cancer through the AKT–GSK3β signaling pathway

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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