TY - JOUR
T1 - Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression
AU - Karp, Cristina M.
AU - Ting, Ting Tan
AU - Mathew, Robin
AU - Nelson, Deidre
AU - Mukherjee, Chandreyee
AU - Degenhardt, Kurt
AU - Karantza-Wadsworth, Vassiliki
AU - White, Eileen
PY - 2008/6/1
Y1 - 2008/6/1
N2 - Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity, and contact inhibition while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
AB - Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity, and contact inhibition while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
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U2 - 10.1158/0008-5472.CAN-07-6814
DO - 10.1158/0008-5472.CAN-07-6814
M3 - Article
C2 - 18519669
AN - SCOPUS:49249121662
SN - 0008-5472
VL - 68
SP - 4105
EP - 4115
JO - Cancer Research
JF - Cancer Research
IS - 11
ER -