SLIT2 inhibits cell migration in colorectal cancer through the AKT-GSK3β signaling pathway
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Updated: May 15, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Wei-Feng Chen1, Wei-Dong Gao, Quan-Lin Li
1Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, 200032, Shanghai, People's Republic of China.
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.
Insights
SLIT2 inhibits colon tumor metastasis by suppressing AKT signaling and epithelial-mesenchymal transition (EMT). This finding highlights SLIT2 as a potential prognostic marker for colorectal cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
- Tumor metastasis remains a significant challenge in CRC treatment.
- Understanding the molecular mechanisms of metastasis is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the functional role of SLIT2 in colon tumor metastasis.
- To elucidate the molecular mechanisms underlying SLIT2's effect on metastasis.
- To evaluate SLIT2 as a potential prognostic marker for colorectal cancer.
Main Methods:
- Immunohistochemistry and molecular assays to assess SLIT2 expression in tumor tissues.
- Cell migration assays (wound-healing, Transwell) to evaluate SLIT2's impact on cell movement.
- Western blotting, immunofluorescence, and AKT inhibition to explore signaling pathways and epithelial-mesenchymal transition (EMT).
Main Results:
- Higher SLIT2 expression correlated with reduced metastasis and improved patient survival.
- SLIT2 inhibited SW480 cell migration and SLIT2 depletion enhanced NCM460 cell migration.
- SLIT2 depletion induced EMT and β-catenin accumulation, effects abrogated by AKT inhibition.
Conclusions:
- SLIT2 suppresses colon tumor metastasis by inhibiting AKT signaling and EMT.
- SLIT2 demonstrates potential as a clinical prognostic marker for colorectal cancer.
- Targeting SLIT2 or its pathways may offer therapeutic strategies for metastatic CRC.
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