Refining the role of Lgl, Dlg and Scrib in Tumor Suppression and Beyond: Learning from the Old Time Classics

Papagiannouli, Fani; Mechler, Bernard M.

doi:10.5772/26017

Cited by 12 publications

(11 citation statements)

References 239 publications

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“…Advances in the diverse functions of dlg, scrib and lgl have defined them as key players in numerous tissues contents and malignancies, and revealed their multitasking role in: junction and cytoskeleton establishment, epithelial cell and planar cell polarity; asymmetric neuroblast division and neuromuscular junctions; cancer initiation and metastasis; cooperation with various signaling pathways in different tissue contexts (Lecuit andWieschaus, 2002, Papagiannouli andMechler, 2012). Similar to other tissues dlg, scrib and lgl play an important role in testis development in the various populations and their cooperation according to the developmental stage can vary significantly.…”

Section: Dlg Scrib and Lgl Act In Common Pathways In Various Tissue mentioning

confidence: 99%

The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma

Papagiannouli¹

2013

Int. J. Dev. Biol.

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Interest in the mechanism leading to the formation of the germline and its differentiation during Drosophila development, initiated even as soon as the first ever cloned tumour suppressor gene in Drosophila, the lethal (2) giant larvae (lgl), had been identified. Further work has shown that the lgl, as well as discs large-1 (dlg) and scribble (scrib) tumor suppressor genes code for scaffolding proteins associated with either the cytoskeletal matrix or the septate junctions that act in common pathways in various tissues. This study analysed the role of Dlg, Scrib and Lgl in the embryonic gonads and testis of Drosophila melanogaster. Loss of scrib, dlg and lgl had no effect on gonad formation, but Dlg and Scrib in the gonadal mesoderm acted critically in the somatic wrapping of the pole cells and the internal structure of the Drosophila embryonic gonads. Dlg also affected the incorporation of the male-specific Sox100B positive mesodermal cells into the male embryonic gonads, yet Sox100B expression in dlg testis remained unaffected. Analysis at later stages revealed that scrib and lgl expression in the somatic lineage of the Drosophila testis, similar to what was previously shown for dlg, was indispensable for testis development and homeostasis, as depletion of these genes resulted in extensive testes defects. The data presented here emphasize the somatic requirement of Scrib, Dlg and Lgl in embryonic gonads, as well as in the Drosophila testis that underlines the importance of the somatic lineage in the establishment and maintenance of testis formation throughout successive developmental stages.

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Section: Dlg Scrib and Lgl Act In Common Pathways In Various Tissue mentioning

confidence: 99%

The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma

Papagiannouli¹

2013

Int. J. Dev. Biol.

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“…The DLG family has important functions governing polarity, cellular structure and growth behavior (16)(17)(18). These functions are thought to be achieved by protein trafficking to the cellular surface of epithelial cells as well as the organization and stabilization of supra-molecular adhesion and signaling complexes through heterodimeric formation (19). Orthologous to the human DLG2 gene is the Drosophila melanogaster DLG gene (dmDLG).…”

Section: Introductionmentioning

confidence: 99%

Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival.

Keane

Améen

Lindlöf

et al. 2020

Preprint

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Neuroblastoma (NB) is a childhood neural crest tumor. There are two groups of aggressive NBs, one with MYCN amplification, and another with 11q chromosomal deletion; these chromosomal aberrations are generally mutually exclusive. The DLG2 gene resides in the 11q-deleted region, thus makes it an interesting NB candidate tumor suppressor gene. Methods We evaluated the association of DLG2 gene expression in NB with patient outcomes, stage and MYCN status, using online microarray data combining independent NB patient data sets. Functional studies were also conducted using NB cell models and the fruit fly. Results Using the array data we concluded that higher DLG2 expression was positively correlated to patient survival. We could also see that expression of DLG2 was inversely correlated with MYCN status and tumor stage. Cell proliferation was lowered in both 11q-normal and 11q-deleted NB cells after DLG2 over expression, and increased in 11q-normal NB cells after DLG2 silencing. Higher level of DLG2 increased the percentage of cells in the G2/M phase and decreased the percentage of cells in the G1 phase. We detected increased protein levels of Cyclin A and Cyclin B in a fruit fly model over expressing dMyc or silencing dmDLG , indicating that both events results in enhanced cell cycling. Induced MYCN expression in NB cells, lowered DLG2 gene expression, this was confirmed in the fly, when dMyc was over expressed, the dmDLG protein level was lowered, indicating a link between Myc over expression and low dmDLG level. Conclusion We conclude that low DLG2 expression level forces cell cycle progression, and that it predicts poor NB patient survival. The low DLG2 expression level could be caused by either MYCN -amplification or 11q-deletion.

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“…The DLG family has important functions governing polarity, cellular structure and growth behavior (18)(19)(20). These functions are thought to be achieved by protein trafficking to the cellular surface of epithelial cells as well as the organization and stabilization of supra-molecular adhesion and signaling complexes through heterodimeric formation (21). Orthologous to the human DLG2 gene is the Drosophila melanogaster DLG gene (dmDLG).…”

Section: Introductionmentioning

confidence: 99%

Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival.

Keane

Améen

Lindlöf

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Neuroblastoma (NB) is a childhood neural crest tumor. There are two groups of aggressive NBs, one with MYCN amplification, and another with 11q chromosomal deletion; these chromosomal aberrations are generally mutually exclusive. The DLG2 gene resides in the 11q-deleted region, thus makes it an interesting NB candidate tumor suppressor gene. Methods We evaluated the association of DLG2 gene expression in NB with patient outcomes, stage and MYCN status, using online microarray data combining independent NB patient data sets. Functional studies were also conducted using NB cell models and the fruit fly. Results Using the array data we concluded that higher DLG2 expression was positively correlated to patient survival. We could also see that expression of DLG2 was inversely correlated with MYCN status and tumor stage. Cell proliferation was lowered in both 11q-normal and 11q-deleted NB cells after DLG2 over expression, and increased in 11q-normal NB cells after DLG2 silencing. Higher level of DLG2 increased the percentage of cells in the G2/M phase and decreased the percentage of cells in the G1 phase. We detected increased protein levels of Cyclin A and Cyclin B in fruit fly models either over expressing dMyc or with RNAi-silenced dmDLG, indicating that both events resulted in enhanced cell cycling. Induced MYCN expression in NB cells, lowered DLG2 gene expression, which was confirmed in the fly; when dMyc was over expressed, the dmDLG protein level was lowered, indicating a link between Myc over expression and low dmDLG level. Conclusion We conclude that low DLG2 expression level forces cell cycle progression, and that it predicts poor NB patient survival. The low DLG2 expression level could be caused by either MYCN -amplification or 11q-deletion.

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Refining the role of Lgl, Dlg and Scrib in Tumor Suppression and Beyond: Learning from the Old Time Classics

Cited by 12 publications

References 239 publications

The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma

The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma

Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival.

Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival.

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