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PMID:17724469

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Citation

Sauermann, M, Sahin, O, Sültmann, H, Hahne, F, Blaszkiewicz, S, Majety, M, Zatloukal, K, Füzesi, L, Poustka, A, Wiemann, S and Arlt, D (2008) Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells. Oncogene 27:1320-6

Abstract

Vacuole membrane protein 1 (Vmp1) is described as a cancer-relevant cell cycle modulator, but the function of this protein and its mode of action in tumor progression are still unknown. In this study, we show that the VMP1 mRNA level is significantly reduced in kidney cancer metastases as compared to primary tumors. Further, VMP1 expression is also decreased in the invasive breast cancer cell lines HCC1954 and MDA-MB-231 as compared to the non-invasive cell lines MCF-12A, T-47D and MCF-7. We show for the first time that Vmp1 is a plasma membrane protein and an essential component of initial cell-cell contacts and tight junction formation. It interacts with the tight junction protein Zonula Occludens-1 and colocalizes in spots between neighboring HEK293 cells. Downregulation of VMP1 by RNAi results in loss of cell adherence, and increases the invasion capacity of the non-invasive kidney cancer cell line Caki-2. In conclusion, our findings establish Vmp1 to be a novel cell-cell adhesion protein and that its expression level determines the invasion and metastatic potential of cancer cells.

Links

PubMed Online version:10.1038/sj.onc.1210743

Keywords

Animals; Breast Neoplasms/chemistry; Breast Neoplasms/genetics; Breast Neoplasms/pathology; COS Cells; Carcinoma, Ductal, Breast/chemistry; Carcinoma, Ductal, Breast/genetics; Carcinoma, Ductal, Breast/pathology; Cell Adhesion/genetics; Cell Communication/genetics; Cell Line; Cell Line, Tumor; Cercopithecus aethiops; Female; Humans; Kidney Neoplasms/chemistry; Kidney Neoplasms/genetics; Kidney Neoplasms/pathology; Membrane Proteins/antagonists & inhibitors; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Neoplasm Invasiveness; Tight Junctions/chemistry; Tight Junctions/metabolism; Tight Junctions/pathology; Tumor Cells, Cultured; Vacuoles/chemistry; Vacuoles/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ZO1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96GC9

F

Seeded From UniProt

complete

HUMAN:BECN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91ZQ0

F

Seeded From UniProt

complete

RAT:VMP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14457

F

Seeded From UniProt

complete

HUMAN:VMP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q07157

F

Seeded From UniProt

complete

HUMAN:VMP1

located_in

GO:0005783: endoplasmic reticulum

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:VMP1

involved_in

GO:0034329: cell junction assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VMP1

involved_in

GO:0098609: cell-cell adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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