title: 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.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Ching-Fong
authors.initials: CF
authors.lastname: Liao
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Lin
authors.forename: Hung-Chang
authors.initials: HC
authors.lastname: Chen
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chang
authors.forename: Li-Tzu
authors.initials: LT
authors.lastname: Li
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Yeh
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Tsu-Han
authors.initials: TH
authors.lastname: Hsu
authors.forename: Shing-Chuan
authors.initials: SC
authors.lastname: Shen
authors.forename: Woan-Ruoh
authors.initials: WR
authors.lastname: Lee
authors.forename: Jeng-Fong
authors.initials: JF
authors.lastname: Chiou
authors.forename: Shue-Fen
authors.initials: SF
authors.lastname: Luo
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D029563:Cellular Apoptosis Susceptibility Protein / Q000097:blood / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000906:Antibodies; D029563:Cellular Apoptosis Susceptibility Protein; D010769:Phosphothreonine; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins