CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression

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• 作者：Ming-Chung Jiang ; Chung-Min Yeh ; Cheng-Jeng Tai ; Hung-Chang Chen ; Shu-Hui Lin ; Tzu-Cheng Su ; Shing-Chuan Shen ; Woan-Ruoh Lee ; Ching-Fong Liao ; Li-Tzu Li ; Ching-Hsiao Lee ; Ying-Chun Chen ; Kun-Tu Yeh ; Chun-Chao Chang
• 关键词：Colorectal cancer ; CSE1L ; K-Ras ; Lymph node ; Metastasis
• 刊名：The American Journal of Surgery
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：206
• 期：3
• 页码：418-427
• 全文大小：2258 K

文摘

Background

Ras plays an important role in colorectal cancer progression. CSE1L (chromosome segregation 1-like) gene maps to 20q13, a chromosomal region that correlates with colorectal cancer development. We investigated the association of CSE1L with Ras in colorectal cancer progression.

Methods

The effect of CSE1L on metastasis-stimulating activity of Ras was studied in an animal model with tumor cells expressing CSE1L-specific shRNA and v-H-Ras. CSE1L expression was evaluated by the immunohistochemical analysis of 127 surgically resected colorectal tumors. K-Ras mutations were analyzed by direct sequencing.

Results

CSE1L knockdown reduced Ras-induced metastasis of B16F10 melanoma cells in C57BL/6 mice. v-H-Ras expression altered the cellular trafficking of CSE1L and increased CSE1L secretion. Most colorectal tumors were positive for CSE1L staining (98.4 % , 125 of 127). Colorectal tumors with K-Ras mutation or high cytoplasmic CSE1L expression were correlated with T status (depth of tumor penetration; P = .004), stage (P = .004), and lymph node metastasis (P = .019).

Conclusions

CSE1L may be a target for treating Ras-associated tumors. Analysis of K-Ras mutation and CSE1L expression may provide valuable clinical and pathological information to aid in the determination of treatment options for colorectal cancer.