Proliferation and polarity in breast cancer: untying the Gordian knot.
Epithelial cancers are associated with genomic instability and alterations in signaling pathways that affect proliferation, apoptosis, and integrity of tissue structure. Overexpression of a number of oncogenic protein kinases has been shown to malignantly transform cells in culture and to cause tumors in vivo, but the interconnected signaling events induced by transformation still awaits detailed dissection. We propose that the network of cellular signaling pathways can be classified into functionally distinct branches, and that these pathways are rewired in transformed cells and tissues after they lose tissue-specific architecture to favor tumor expansion and invasion. Using three-dimensional (3D) culture systems, we recently demonstrated that polarity and proliferation of human mammary epithelial cancer cells were separable consequences of signaling pathways downstream of PI3 kinase. These, and results from a number of other laboratories are beginning to provide insight into how different signaling pathways may become interconnected in normal tissues to allow homeostasis, and how they are disrupted during malignant progression.
Liu
Hong
H
Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Radisky
Derek C
DC
Bissell
Mina J
MJ
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods; D016764:Cell Polarity; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein