Src through mediation of EGFR, and PRKCD. This interaction is antagonized by degradation of beta-catenin by GSK3B. MUC1 blocks the phosphorylation-dependent degradation of beta-catenin by GSK3B. The end result is that increased expression of MUC1 in cancer increases stabilized beta-catenin. This promotes the expression of vimentin and CDH2. These proteins are associated with a mesenchymal phenotype, characterized by increased motility and invasiveness. In cancer cells, increased expression of MUC1 promotes cancer cell invasion through beta-catenin, resulting in the initiation of epithelial-mesenchymal transition which promotes the formation of metastases. Diagnostic uses Blood tests: Cancer Antigens (CA) 27.29 and 15-3 CA 27.29 (aka BR 27.29) and CA 15-3 measure different epitopes of the same protein antigen product of the MUC1 gene seen in breast cancer. CA 27.29 has enhanced sensitivity and specificity compared to CA 15-3 and is elevated in 30% of patients with low-stage disease and 60 to 70% of patients with advanced-stage breast cancer. CA 27.29 levels over 100 U/mL and CA 15-3 levels over 25 U/mL are rare in benign conditions and suggest malignancy. Immunohistochemistry Using immunohistochemistry, MUC1 can be identified in a wide range of secretory epithelia and their neoplastic equivalents: It is a marker of various types of cancer (see below). In micropapillary carcinoma of the breast and bladder, MUC1 stains the stroma-facing surface of cell clusters of micropapillary units. It can distinguish systemic anaplastic large cell lymphoma (MUC1 positive) from cutaneous anaplastic large cell lymphoma (usually MUC1 negative). Although other antibodies, such as cytokeratins, are more commonly used for the identification of metastatic carcinoma deposits, EMA can be used to distinguish mesothelioma, in which it is restricted to the cell membranes and associated micovilli, from adenocarcinoma, in which it is diffusely spread through the cytoplasm. Diseases with positive MUC1 staining Adenocarcinomas Breast cancer Colorectal cancer Pancreatic cancer Carcinoid tumor, chordoma Choriocarcinoma Desmoplastic small-round-cell tumor Epithelioid sarcoma Follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, reticulum cell sarcoma Lung: Type II cell lesions (hyperplasia, dysplasia) Lymphomas Anaplastic large-cell lymphoma Diffuse large B-cell lymphoma (variable expression) Plasmablastic lymphoma Primary effusion lymphoma Meningioma Mesotheliomas (epithelioid) Myeloma Paget's disease of the breast Perineurioma Plasmacytomas Renal cell carcinoma Synovial sarcoma (epithelial areas) Thymic carcinoma (often) Negative staining Myoepithelial cells Adrenocortical carcinoma Hepatocellular carcinoma Germ cell tumors (except choriocarcinoma) Acquired cystic kidney disease-associated renal cell carcinoma Leiomyosarcoma (usually) Liposarcoma Melanoma Neuroblastoma Paraganglioma Solitary fibrous tumor Normal tissues with positive staining Apical surface