Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway.

Abstract

BACKGROUND:

Neuron navigator 2 (NAV2) encodes a member of the neuron navigator gene family, which plays a role in tumorigenesis and cell migration. However, the prognostic value of NAV2 expression in colorectal cancer (CRC) patients and the potential pathway through which NAV2 promotes migration and invasion in CRC cell lines is poorly understood.

METHODS:

The expression level of NAV2 was detected in CRC tissues from two different CRC cohorts by immunohistochemistry, qRT-PCR and Western blotting; the correlation between NAV2 expression and clinicopathological characters was analyzed, and the prognostic value of NAV2 expression was analyzed using a Cox regression model. CRC cell lines with NAV2 knocked out were used to validate the function and potential pathway used by NAV2 to promote CRC cell migration and invasion.

RESULTS:

The results showed that NAV2 was overexpressed in CRC tissues, and it was closely correlated with depth of invasion, and lymph and distant metastasis. Multivariate analysis indicated that high NAV2 expression was a poor prognostic indicator of recurrence-free survival and overall survival in CRC patients. Furthermore, Cox regression analysis revealed that high NAV2 expression integrated with high tumor budding grade was a powerful independent predictive factor of CRC clinical outcome. In vitro and in vivo assays demonstrated that knockdown of NAV2 led to reduced migration and invasion of cancer cells, and the process involved the regulation of F-actin polymerization through the SSH1L/cofilin-1 pathway.

CONCLUSION:

Based on these findings, NAV2 could serve as both a prognostic biomarker and a potential therapeutic target for patients with NAV2-positive CRC.

• Authors: Fengbo Tan, Hong Zhu, Yiming Tao, Nanhui Yu, Qian Pei, Heli Liu, Yuan Zhou, Haifan Xu, Xiangping Song, Yuqiang Li, Zhongyi Zhou, Xiao He, Xingwen Zhang, Haiping Pei
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 34 Pg. 117 (Oct 09 2015) ISSN: 1756-9966 [Electronic] England
• PMID: 26452645 (Publication Type: Journal Article)

Chemical References

• Actins
• Cofilin 1
• Nerve Tissue Proteins
• RNA, Small Interfering
• Phosphoprotein Phosphatases
• SSH1 protein, human
• DNA Helicases
• NAV2 protein, human

Topics

• Actins (metabolism)
• Aged
• Animals
• Caco-2 Cells
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Transformation, Neoplastic (genetics)
• Cofilin 1 (metabolism)
• Colorectal Neoplasms (genetics, mortality, pathology)
• DNA Helicases
• Disease-Free Survival
• Female
• HCT116 Cells
• Hep G2 Cells
• Humans
• Lymphatic Metastasis (genetics, pathology)
• Male
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Transplantation
• Nerve Tissue Proteins (biosynthesis, genetics)
• Phosphoprotein Phosphatases (metabolism)
• RNA Interference
• RNA, Small Interfering (genetics)
• Transplantation, Heterologous
• Treatment Outcome