Loss of apico-basal polarity is one of the crucial factors that drives epithelial tumor progression, scribbleldiscs largellethal giant larvae (scrib/dlg/lgl), a group of apico-basal polarity genes, were initially id...Loss of apico-basal polarity is one of the crucial factors that drives epithelial tumor progression, scribbleldiscs largellethal giant larvae (scrib/dlg/lgl), a group of apico-basal polarity genes, were initially identified as members of "neoplastic" tumor-suppressors in flies. The components of the Hippo signaling pathway, which is crucial for organ size control and cancer development, were also identified through Drosophila genetic screens as members of "hyperplastic" tumor-suppressors. Accumulating evidence in recent studies implies that these two tumor-suppressor signaling pathways are not mutually exclusive but rather cooperatively act to give rise to highly malignant tumors. The interaction of these tumor-suppressor pathways could include deregulations of actin cytoskeleton, cell-cell contact, and apical-domain size of展开更多
The lethal giant larvae(lgl)gene was first identified more than 30 years ago in Drosophila and characterized as a tumor suppressor gene.Studies in budding yeast,flies and mammals all indicate that the evolutionarily c...The lethal giant larvae(lgl)gene was first identified more than 30 years ago in Drosophila and characterized as a tumor suppressor gene.Studies in budding yeast,flies and mammals all indicate that the evolutionarily conserved Lgl family proteins play an important role in cell polarity.Sro7/77,the yeast Lgl homologues,are important for the establishment and reinforcement of cell polarity through their localized interaction and kinetic activation of the post-Golgi secretion machinery.As for higher eukaryotes,both in epithelial polarity and asymmetric cell division,the role of Lgl protein is deployed by localizing proteins to the membrane in a polarized fashion.In addition,Lgl is transiently required during the establishment phase of polarity,implicating that Lgl functions at strategic time points for proliferation control.Studies in cancer biology provide direct connections between malfunction of Lgl and formation,progression and metastasis of various cancers.Here,we review recent advances in the field,focusing on the function of the Lgl family in cellular polarization.展开更多
文摘Loss of apico-basal polarity is one of the crucial factors that drives epithelial tumor progression, scribbleldiscs largellethal giant larvae (scrib/dlg/lgl), a group of apico-basal polarity genes, were initially identified as members of "neoplastic" tumor-suppressors in flies. The components of the Hippo signaling pathway, which is crucial for organ size control and cancer development, were also identified through Drosophila genetic screens as members of "hyperplastic" tumor-suppressors. Accumulating evidence in recent studies implies that these two tumor-suppressor signaling pathways are not mutually exclusive but rather cooperatively act to give rise to highly malignant tumors. The interaction of these tumor-suppressor pathways could include deregulations of actin cytoskeleton, cell-cell contact, and apical-domain size of
基金This work was supported by grants from the National Science Foundation of China(Grant No.30900720)Tian Jin Science Foundation(No.09JCYBJC09000)to Puyue WANG.
文摘The lethal giant larvae(lgl)gene was first identified more than 30 years ago in Drosophila and characterized as a tumor suppressor gene.Studies in budding yeast,flies and mammals all indicate that the evolutionarily conserved Lgl family proteins play an important role in cell polarity.Sro7/77,the yeast Lgl homologues,are important for the establishment and reinforcement of cell polarity through their localized interaction and kinetic activation of the post-Golgi secretion machinery.As for higher eukaryotes,both in epithelial polarity and asymmetric cell division,the role of Lgl protein is deployed by localizing proteins to the membrane in a polarized fashion.In addition,Lgl is transiently required during the establishment phase of polarity,implicating that Lgl functions at strategic time points for proliferation control.Studies in cancer biology provide direct connections between malfunction of Lgl and formation,progression and metastasis of various cancers.Here,we review recent advances in the field,focusing on the function of the Lgl family in cellular polarization.