a new co-conspirator with her2 and her3---muc-4 which also serves as cloaking device

[Lani]

making her2+ bc invisible from the immune system. This article discusses two other ways muc-4 makes her2+ breast cancer more aggressive by helping it migrate.

This new finding that muc-4 acts like a coconspirator may help explain the mystery of why they never found a ligand for her2 (receptors like her2 evolve like a lock for which the ligand is the key--a key for the her2 lock has never been found)
:
J Cell Physiol. 2010 Apr 21. [Epub ahead of print]
Mechanistic and signaling analysis of Muc4-ErbB2 signaling module: New insights into the mechanism of ligand-independent ErbB2 activity.
Kozloski GA, Carraway CA, Carraway KL.

Department of Biochemistry and Molecular Biology, University of Miami, Miller School of Medicine, Miami, Florida.
Abstract
The membrane mucin Muc4 is aberrantly expressed in numerous epithelial carcinomas and is currently used as a cancer diagnostic and prognostic tool. Muc4 can also potentiate signal transduction by modulating differential ErbB2 phosphorylation in the absence and in the presence of the ErbB3 soluble ligand heregulin (HRG-beta1). These features of Muc4 suggest that Muc4 is not merely a cancer marker, but an oncogenic factor with a unique-binding/activation relationship with the receptor ErbB2. In the present study, we examined the signaling mechanisms that are associated with the Muc4-ErbB2 module by analyzing ErbB2 differential signaling in response to Muc4 expression. Our study was carried out in the A375 human melanoma and BT-474 breast cancer cell lines as our model systems. Quantitative and comparative signaling modulations were evaluated by immunoblot using phospho-specific antibodies, and densitometry analysis. Signaling complex components were identified by chemical cross-linking, fractionation by gel filtration, immunoprecipitation, and immunoblotting. Activated downstream signaling pathways were analyzed by an antibody microarray screen and immunoblot analyses. Our results indicate that Muc4 modulates ErbB2 signaling potential significantly by stabilizing and directly interacting with the ErbB2-ErbB3 heterodimer. Further analyses indicate that Muc4 promotes ErbB2 autocatalysis, but it has no effect on ErbB3 phosphorylation, although the chemical cross-linking data indicated that the signaling module is composed of Muc4, ErbB2, and ErbB3. Our microarray analysis indicates that Muc4 expression promotes cell migration by increasing the phosphorylation of the focal adhesion kinase and also through an increase in the levels of beta-catenin. J. Cell. Physiol. (c) 2010 Wiley-Liss, Inc.

PMID: 20432461

Hopefully muc-4 will become a new target.

[suzan w]

muc- does this have anything to do with mucus? or over-production of the stuff>>