A cross-linking assay allows the detection of receptors for the somatostatin analogue, lanreotide in human breast tumours

Abstract Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models. In human breast tumours, the EMT-transcription factors strongly correlate with activated Hedgehog/GLI signalling but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis via non-cell autonomous effects that activate the Hh pathway. Although all Hh inhibitors may act against tumours with canonical Hh/GLI signalling, only GLI inhibitors would act against non-canonical EMT-induced GLI activation.

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Protein arginine methyltransferase 6-dependent gene expression and splicing: association with breast cancer outcomes

Endocrine Related Cancer ◽

10.1530/erc-12-0100 ◽

2012 ◽

Vol 19 (4) ◽

pp. 509-526 ◽

Cited By ~ 16

Author(s):

Dennis H Dowhan ◽

Matthew J Harrison ◽

Natalie A Eriksson ◽

Peter Bailey ◽

Michael A Pearen ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Alternative Splicing ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Gene Expression Signature ◽

Human Breast ◽

Arginine Methyltransferase ◽

Breast Tumours

Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing and is implicated in endocrine system development and function, cell death, cell cycle, gene expression and cancer. Despite its role in these processes, little is known about its function and cellular targets in breast cancer. To identify novel gene targets regulated by PRMT6 in breast cancer cells, we used a combination of small interfering RNA and exon-specific microarray profilingin vitrocoupled toin vivovalidation in normal breast and primary human breast tumours. This approach, which allows the examination of genome-wide changes in individual exon usage and total transcript levels, demonstrated thatPRMT6knockdown significantly affected i) the transcription of 159 genes and ii) alternate splicing of 449 genes. ThePRMT6-dependent transcriptional and alternative splicing targets identifiedin vitrowere validated in human breast tumours. Using the list of genes differentially expressed between normal andPRMT6knockdown cells, we generated aPRMT6-dependent gene expression signature that provides an indication of PRMT6 dysfunction in breast cancer cells. Interrogation of several well-studied breast cancer microarray expression datasets with thePRMT6gene expression signature demonstrated that PRMT6 dysfunction is associated with better overall relapse-free and distant metastasis-free survival in the oestrogen receptor (ER (ESR1)) breast cancer subgroup. These results suggest that dysregulation ofPRMT6-dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile.

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A cysteine proteinase secreted from human breast tumours is immunologically related to cathepsin B

Biochemical Journal ◽

10.1042/bj2070633 ◽

1982 ◽

Vol 207 (3) ◽

pp. 633-636 ◽

Cited By ~ 39

Author(s):

A D Recklies ◽

A R Poole ◽

J S Mort

Keyword(s):

Cathepsin B ◽

Human Liver ◽

Cysteine Proteinase ◽

Human Breast ◽

Breast Tumours ◽

Monospecific Antiserum ◽

Thiol Proteinase

The stable cathepsin B-like cysteine (thiol) proteinase secreted from human breast tumours in culture was shown to be destabilized by mercurial compounds. After such treatment the enzyme cross-reacts in a radioimmunoassay with a monospecific antiserum to human liver cathepsin B. It is suggested that the secreted enzyme may be a precursor form of lysosomal cathepsin B.

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