Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells

Sheng, Zejuan; Sun, Wenping; Smith, Elizabeth; Cohen, Cynthia; Sheng, Zeqi; Xu, Xiang Xi

doi:10.1038/sj.onc.1203853

Cited by 76 publications

(93 citation statements)

References 35 publications

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“…Since Dab2 is a candidate tumor-suppressor gene product (Mok et al, 1994;Fulop et al, 1998;Fazili et al, 1999) and is known to inhibit cell growth and proliferation in various cell types (Fulop et al, 1998;Mok et al, 1998;Tseng et al, 1999;Sheng et al, 2000;He et al, 2001b;Smith et al, 2001;Wang et al, 2001), the observation that its phosphorylation state and interactions with other proteins can change during the cell cycle is of interest. Cyclin-dependent kinases are known to phosphorylate many proteins that regulate the rate of progression through the cell cycle and exert reciprocal effects on cyclin-dependent kinase activity (Ferrell, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations to Dab1 underlie the abnormal brain development observed in the mutant strains of mice known as scrambler and yotari (Howell et al, 1997b;Sheldon et al, 1997;Ware et al, 1997), suggesting a role for Dab1 in neural development similar to that of Drosophila Dab. In contrast, Dab2 plays no known role in neural development, but rather is considered a candidate tumor suppressor because it is downregulated in various types of tumor (Mok et al, 1994;Fulop et al, 1998;Fazili et al, 1999) and is capable of strongly inhibiting cell growth and proliferation in many cell types (Fulop et al, 1998;Mok et al, 1998;Tseng et al, 1999;Sheng et al, 2000;He et al, 2001b;Smith et al, 2001;Wang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

et al. 2003

Oncogene

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Disabled-2 (Dab2; also known as p96 and DOC-2) is a signal transduction protein that has been implicated in the control of cell growth. Dab2 is known to be a phosphoprotein, but little is known about the kinases that phosphorylate Dab2. We have found that Dab2 phosphorylation is markedly increased during the mitosis phase of the cell cycle. This phosphorylation is blocked by roscovitine, a selective inhibitor of cyclin-dependent kinases. Dab2 robustly coimmunoprecipitates from cells with the cyclin-dependent kinase cdc2, and purified cdc2 can phosphorylate purified Dab2 fusion proteins in vitro on multiple sites. Cellular phosphorylation of Dab2 by cdc2 promotes the association of Dab2 with Pin1, a peptidylprolyl isomerase that regulates the rate of Dab2 dephosphorylation. These findings reveal that Dab2 is differentially phosphorylated during the cell cycle by cdc2 and provide a potential feedback mechanism by which Dab2 inhibition of cell growth and proliferation may be regulated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

et al. 2003

Oncogene

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“…In normal tissues, DOC-2/hDab-2 expression is distributed in the surface epithelial cells of ovary or the ductal epithelial cells of breast (Fazili et al, 1999;Mok et al, 1994Mok et al, , 1998Sheng et al, 2000). Loss of DOC-2/hDab-2 expression in ovarian cancer appears to be an early tumorigenesis event in serous but not mucinous ovarian cancer (Fazili et al, 1999;Mok et al, 1998).…”

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confidence: 99%

“…Loss of DOC-2/hDab-2 expression in ovarian cancer appears to be an early tumorigenesis event in serous but not mucinous ovarian cancer (Fazili et al, 1999;Mok et al, 1998). It has been reported that DOC-2/hDab-2 expression is correlated with the presence of basement membrane in ovarian and breast tumors, suggesting that DOC-2/hDab-2 exerts its anti-tumor function by controlling the positioning of the epithelial cells to basement membrane (Sheng et al, 2000). Consistently, reconstitution of DOC-2/hDab-2 expression in human ovarian cancer cells resulted in reduction of growth rate in culture and tumorigenicity in nude mice (Mok et al, 1998).…”

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DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway

et al. 2001

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DOC-2/hDab-2 was identi®ed due to the loss of its expression in primary ovarian cancer cells. It is believed that loss of DOC-2/hDab-2 expression is one of the early events of ovarian malignancy. These results suggest a function of DOC-2/hDab-2 as a tumor suppressor. However, it is not clear how DOC-2/hDab-2 negatively regulates cancer cell growth. In this report, we demonstrate that DOC-2/hDab-2 expression in breast cancer cells resulted in sensitivity to suspension-induced cell death (anoikis). This event was associated with the down-regulation of the integrin-linked kinase (ILK) activity. Since ILK is a key factor in regulating the cellular signaling in responding to the extracellular signals through adhesion molecules like integrins, our results indicate that DOC-2/hDab-2 may prevent tumor growth and invasion by modulating the anti-apoptotic ILK pathway. Oncogene (2001) 20, 6960 ± 6964.

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Preparation of water‐soluble syndiotacticity‐rich high molecular weight poly(vinyl alcohol) microfibrillar fibers using copolymerization of vinyl pivalate and vinyl acetate and saponification

Lyoo

Yeum

et al. 2003

J of Applied Polymer Sci

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Water-soluble high molecular weight (HMW) syndiotactic poly(vinyl alcohol) (s-PVA) microfibrillar fibers were prepared by the saponification with various conditions such as amount of alkali solution, saponification temperature, and saponification concentration from copoly-(vinyl pivalate (VPi)/vinyl acetate (VAc)) copolymerized using various VPi/VAc feed ratios. To produce s-PVA microbrillar fibers having various water-soluble temperatures for many industrial applications, the intrinsic viscosities, syndiotactic diad (S-diad) contents, and degrees of saponification (DS)s of PVAs were finely controlled to 1.2-3.6 dL/g, 56.3-58.3%, and 91.4 -98.3%, respectively. Through a series of experiments, it was found that the amount of alkali may alter the structure of the saponified polymers, primarily the DS, and the structural variation changes viscosity. That is, intrinsic viscosity was sharply decreased as the amount of alkali solution was increased. DS was increased with an increase in the amount of alkali solution. S-diad content was increased with an increase in the VPi content. HMW s-PVA microfibrillar fibers having S-diad content of 56.3-58.3% prepared by the saponification of copoly(VPi/VAc) were completely soluble in water at 100°C.

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Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells

Cited by 76 publications

References 35 publications

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway

Preparation of water‐soluble syndiotacticity‐rich high molecular weight poly(vinyl alcohol) microfibrillar fibers using copolymerization of vinyl pivalate and vinyl acetate and saponification

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