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

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.

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