MIEN1 (migration and invasion enhancer 1)

2012-12-01   Elad Katz 

Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK

Identity

HGNC
LOCATION
17q12
LOCUSID
ALIAS
C17orf37,C35,ORB3,RDX12,XTP4
FUSION GENES

DNA/RNA

Description

MIEN1 DNA contains 4 coding exons over 1,63 kb on the minus strand between ERBB2 and GRB7 on human chromosome 17q12. It is also neighbouring mRNA4728.

Transcription

Transcript (NC_000017.100) length: 1006 bps. Transcription was reported in a variety of cell lines and organs, mainly using gene expression arrays (EMBL-EBI).

Pseudogene

None identified.

Proteins

Description

MIEN1 is a small (12 kDa) membrane bound protein found in a variety of human tumours (Evans et al., 2006). Its main function is to induce cell invasion and it may be involved in metastasis (Dasgupta et al., 2011; Dasgupta and Vishwanatha, 2007; Katz et al., 2010).

Expression

MIEN1 is almost exclusively expressed in human tumours, with the notable exception of Leydig cells in testes (Evans et al., 2006).

Localisation

MIEN1 protein is membrane bound and its stability depends on its localization (our unpublished observations). MIEN1 contains a CVIL amino acid sequence in the C-terminal, which fits the prenylation motif CaaX (Evans et al., 2006). Based on several physical properties, such as size, flexibility, membrane buried preference, and presence of leucine as the X residue, MIEN1 is predicted to be geranylgeranylated in vivo by GGTI enzyme, resulting in the addition of 20-carbon isoprenoid moiety.
Atlas Image
With permission by Hsu et al. (Hsu et al., 2012).

Function

The MIEN1 sequence EATYLELASAVKEQYPGIEI conforms to a prototypical immuno-receptor tyrosine-based activation motif (ITAM). ITAMs, such as this of C35 rely on Syk protein kinase for their signaling capacities (Katz et al., 2010). The most commonly reported consequence of MIEN1 over-expression is the induction of cell motility and invasion (Dasgupta et al., 2011; Katz et al., 2010). High levels of MIEN1 expression lead to epithelial to mesenchymal transition in breast cell lines (Katz et al., 2011a). However, intermediate levels lead to a cancer phenomenon rarely observed in experimental models, collective invasion (Katz et al., 2011b).

Homology

MIEN1 is very highly conserved among six higher eukaryotic species (identities >77%) but does not seem to have orthologues in microbial organisms (Evans et al., 2006). MIEN1 contains an ITAM motif which is prevalent in immune receptors as well as oncogenic viruses.

Mutations

Note

A single SNP, rs3809717, was described with no bearing on breast cancer risk (attributed originally to the ERBB2 gene, (Einarsdóttir et al., 2006)).

Implicated in

Entity name
Carcinomas
Note
Several carcinomas (breast, ovarian, and gastro-intestinal cancers) show high expression of the ERBB2 amplicon containing the MIEN1 gene.
Entity name
Breast cancer
Disease
Over-expression of ERBB2 amplicon is seen in ~20% of breast cancers and it confers worse biological behavior and clinical aggressiveness in breast cancer. Breast cancers can have up to 25 to 50 copies of the ERBB2 amplicon. MIEN1 is one of the core ERBB2 genes which are always over-expressed with ERBB2/HER2 (Kauraniemi et al., 2003).
Prognosis
The prognosis of MIEN1 over-expressing breast cancer is indistinguishable from those of ERBB2 over-expressing breast cancers, due to the common amplification (Katz et al., 2010).
Entity name
Prostate cancer
Disease
MIEN1 is highly overexpressed in prostate cancer, where it modulates the Akt activity as a membrane bound adapter protein (Dasgupta et al., 2009). MIEN1 is post-translationaly modified by addition of prenyl groups that translocates the protein to the inner face of the plasma membrane. Ectopic expression of MIEN1 activates Akt and cascades downstream signaling through NF-κB pathway upregulating expression of several migratory and invasive genes (Dasgupta et al., 2011). MIEN1 may act as a scaffolding protein blocking PTEN binding to Akt; however, the exact mechanism is not known.
Prognosis
Unkown.

Bibliography

Pubmed IDLast YearTitleAuthors
216284592011Prenylated c17orf37 induces filopodia formation to promote cell migration and metastasis.Dasgupta S et al
171321592006Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study.Einarsdóttir K et al
171219402006C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer.Evans EE et al
232849732012Solution structure of the oncogenic MIEN1 protein reveals a thioredoxin-like fold with a redox-active motif.Hsu CH et al
213472352011An in vitro model that recapitulates the epithelial to mesenchymal transition (EMT) in human breast cancer.Katz E et al
214831022011An analytical approach differentiates between individual and collective cancer invasion.Katz E et al
145781972003Amplification of a 280-kilobase core region at the ERBB2 locus leads to activation of two hypothetical proteins in breast cancer.Kauraniemi P et al

Other Information

Locus ID:

NCBI: 84299
MIM: 611802
HGNC: 28230
Ensembl: ENSG00000141741

Variants:

dbSNP: 84299
ClinVar: 84299
TCGA: ENSG00000141741
COSMIC: MIEN1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000141741ENST00000394231Q9BRT3
ENSG00000141741ENST00000577810J3KTI2

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
254069432014MicroRNA-940 suppresses prostate cancer migration and invasion by regulating MIEN1.29
195030952009Novel gene C17orf37 in 17q12 amplicon promotes migration and invasion of prostate cancer cells.24
191245062009Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer.22
150108122004Evolutionary recombination hotspot around GSDML-GSDM locus is closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon.16
171171802006HapMap-based study of the 17q21 ERBB2 amplicon in susceptibility to breast cancer.16
262727942015MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression.16
216284592011Prenylated c17orf37 induces filopodia formation to promote cell migration and metastasis.15
268278262016MicroRNA-26b suppresses the metastasis of non-small cell lung cancer by targeting MIEN1 via NF-κB/MMP-9/VEGF pathways.14
259965852015MIEN1 promotes oral cancer progression and implicates poor overall survival.11
238808252013The interaction between C35 and ΔNp73 promotes chemo-resistance in ovarian cancer cells.10

Citation

Elad Katz

MIEN1 (migration and invasion enhancer 1)

Atlas Genet Cytogenet Oncol Haematol. 2012-12-01

Online version: http://atlasgeneticsoncology.org/gene/52476/mien1