Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control.
The polarized glandular organization of epithelial cells is frequently lost during development of carcinoma. However, the specific oncogene targets responsible for polarity disruption have not been identified. Here, we demonstrate that activation of ErbB2 disrupts apical-basal polarity by associating with Par6-aPKC, components of the Par polarity complex. Inhibition of interaction between Par6 and aPKC blocked the ability of ErbB2 to disrupt the acinar organization of breast epithelia and to protect cells from apoptosis but was not required for cell proliferation. Therefore, oncogenes target polarity proteins to disrupt glandular organization and protect cells from apoptotic death during development of carcinoma.
Aranda
Victoria
V
Cold Spring Harbor Laboratory,One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Haire
Teresa
T
Nolan
Marissa E
ME
Calarco
Joseph P
JP
Rosenberg
Avi Z
AZ
Fawcett
James P
JP
Pawson
Tony
T
Muthuswamy
Senthil K
SK
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D002352:Carrier Proteins; D011493:Protein Kinase C; D018719:Erb-b2 Receptor Tyrosine Kinases; C115015:PKC-3 protein