Induction of E-cadherin endocytosis by loss of protein phosphatase 2A expression in human breast cancers.
The cell-cell adhesion molecule E-cadherin is stabilized by linking intracellularly with the actin cytoskeleton through PP2A-mediated recruitment of IQGAP1 to Rac1-bound E-cadherin-catenins complex in nonmalignant HME cells. However, little is known about the dysfunction of E-cadherin by loss or reduced expression of PP2A in human breast cancer cells. We report here that both human breast cancer MDA-MB-231 and MCF-7 cells were deficient in expression of the PP2A-A protein and lost the IQGAP1 recruitment to Rac1-bound catenins. In MDA-MB-231 cells, E-cadherin was also deficient. Immunohistochemical analysis of the normal-carcinoma matched human breast tissue arrays revealed that PP2A-A was expressed in 96% of normal tissue specimens but not in 57% of carcinoma specimens. Expression of E-cadherin in MCF-7 cells was 1.5-fold higher than that in HME cells, however, 80% of E-cadherin was endocytosed and incompletely anchored to F-actin. Therefore, we propose that the dysfunction of E-cadherin due to its endocytosis may occur in some proportion of human breast carcinomas in which the PP2A-A protein is lost or significantly reduced.
Suzuki
Katsuo
K
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
Takahashi
Kazuhide
K
D000199:Actins / Q000737:chemistry; D019921:Biotinylation; D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D054648:Protein Phosphatase 2; D014018:Tissue Distribution; D020703:ras GTPase-Activating Proteins / Q000737:chemistry
D000199:Actins; D015820:Cadherins; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2