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CSE1L, a novel microvesicle membrane protein, mediates Ras-triggered microvesicle generation and metastasis of tumor cells.


ABSTRACT: Tumor-derived microvesicles are rich in metastasis-related proteases and play a role in the interactions between tumor cells and tumor microenvironment in tumor metastasis. Because shed microvesicles may remain in the extracellular environment around tumor cells, the microvesicle membrane protein may be the potential target for cancer therapy. Here we report that chromosome segregation 1-like (CSE1L) protein is a microvesicle membrane protein and is a potential target for cancer therapy. v-H-Ras expression induced extracellular signal-regulated kinase (ERK)-dependent CSE1L phosphorylation and microvesicle biogenesis in various cancer cells. CSE1L overexpression also triggered microvesicle generation, and CSE1L knockdown diminished v-H-Ras-induced microvesicle generation, matrix metalloproteinase (MMP)-2 and MMP-9 secretion and metastasis of B16F10 melanoma cells. CSE1L was preferentially accumulated in microvesicles and was located in the microvesicle membrane. Furthermore, anti-CSE1L antibody-conjugated quantum dots could target tumors in animal models. Our findings highlight a novel role of Ras-ERK signaling in tumor progression and suggest that CSE1L may be involved in the "early" and "late" metastasis of tumor cells in tumorigenesis. Furthermore, the novel microvesicle membrane protein, CSE1L, may have clinical utility in cancer diagnosis and targeted cancer therapy.

SUBMITTER: Liao CF 

PROVIDER: S-EPMC3521793 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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CSE1L, a novel microvesicle membrane protein, mediates Ras-triggered microvesicle generation and metastasis of tumor cells.

Liao Ching-Fong CF   Lin Shu-Hui SH   Chen Hung-Chang HC   Tai Cheng-Jeng CJ   Chang Chun-Chao CC   Li Li-Tzu LT   Yeh Chung-Min CM   Yeh Kun-Tu KT   Chen Ying-Chun YC   Hsu Tsu-Han TH   Shen Shing-Chuan SC   Lee Woan-Ruoh WR   Chiou Jeng-Fong JF   Luo Shue-Fen SF   Jiang Ming-Chung MC  

Molecular medicine (Cambridge, Mass.) 20121206


Tumor-derived microvesicles are rich in metastasis-related proteases and play a role in the interactions between tumor cells and tumor microenvironment in tumor metastasis. Because shed microvesicles may remain in the extracellular environment around tumor cells, the microvesicle membrane protein may be the potential target for cancer therapy. Here we report that chromosome segregation 1-like (CSE1L) protein is a microvesicle membrane protein and is a potential target for cancer therapy. v-H-Ras  ...[more]

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