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Signal transduction of fertilization in frog eggs and anti-apoptotic mechanism in human cancer cells: common and specific functions of membrane microdomains.

Sato K - Open Biochem J (2008)

Bottom Line: Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein.Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus.Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cell and Developmental Biology, Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan. kksato@cc.kyoto-su.ac.jp

ABSTRACT
Membrane microdomains or lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of lipids (e.g. cholesterol, sphingolipids) and proteins (e.g. glycosylphosphatidylinositol-anchored proteins, growth factor receptor/kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein. Protease activity toward uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of uroplakin III seems to be catalyzed by the egg tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called 'egg activation'. Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder carcinoma cells.

No MeSH data available.


Related in: MedlinePlus

Initiation, promotion and progression of carcinogenesis: from benign tumor to malignant tumor. (A) Survival and growth under microenvironment where no supply of energy and nutrient is available. Serum starvation in cell culture may mimic such a microenvironment in vitro. (B) Anti-apoptotic mechanism of cancer cells. Cell become invasive and enter newly formed capillary (induction of angiogenesis). (C) Newly formed capillary supports growth and survival of tumor. Cells travel through bloodstream and undergo metastasis. This scheme is adapted from “ The Bi9ology of Cancer” by R.A. Weinberg (Garland Science, 2007).
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Figure 3: Initiation, promotion and progression of carcinogenesis: from benign tumor to malignant tumor. (A) Survival and growth under microenvironment where no supply of energy and nutrient is available. Serum starvation in cell culture may mimic such a microenvironment in vitro. (B) Anti-apoptotic mechanism of cancer cells. Cell become invasive and enter newly formed capillary (induction of angiogenesis). (C) Newly formed capillary supports growth and survival of tumor. Cells travel through bloodstream and undergo metastasis. This scheme is adapted from “ The Bi9ology of Cancer” by R.A. Weinberg (Garland Science, 2007).

Mentions: There are several experimental conditions that promote apoptosis in cultured cancer cells. They include application of Fas ligand, a death inducer, or anti-Fas antibody, hypoxia, hydrogen peroxide, irradiation, and chemical inhibitors for metabolic enzymes or signaling pathways etc. [87-89]. Serum starvation serves as one of such pro-apoptotic cellular conditions examined to date. At the initial stage of carcinogenesis, cancer cells are not necessarily surrounded by capillary system. Under such microenvironment, however, cancer cells can proliferate effectively; thereby they are capable of inducing angiogenesis that will help cancer cells to populate more and to undergo invasion and metastasis (Fig. 3). We have employed human bladder carcinoma cell line 5637 as a model cell system to analyze molecular mechanism of serum starvation-resistant growth of cancer cells [90-92]. Survival and growth of this cell line in serum-free conditions have been reported to involve the actions of ligands for epidermal growth factor receptor/kinase (EGFR/kinase) [93], suggesting that protein tyrosine phosphorylation plays a central part of survival signaling. In support of this, immunoblotting with anti-phosphotyrosine antibody has demonstrated that a number of proteins become tyrosine-phosphorylated in response to serum starvation [94]. Interestingly, time course of increase in tyrosine phosphorylation is quite slow; about eight hours are required for its plateau phase, indicating that up-regulation of EGFR/kinase ligands, if any, may need some hours to be promoted. Immunoprecipitation studies have demonstrated that 170-kDa EGFR/kinase is tyrosine-phosphorylated in serum-starved 5637 cells; however, it is different from a more prominently tyrosine-phosphorylated protein of 145 kDa. Mass spectrometric analysis has demonstrated that it is β-subunit of hepatocyte growth factor receptor/kinase (HGFR/kinase or c-Met). Although HGFR/kinase and its cognate high affinity ligand HGF/scatter factor (SF) have been originally identified in liver cells (hepatocytes), they are ubiquitously expressed in many kinds of cells and tissues, and implicated in a number of cellular functions (growth, differentiation, apoptosis etc.) [95,96]. Therefore, it is possible to think that, in addition to EGFR/kinase and its ligands, HGFR/kinase and HGF/SF are involved in the survival mechanism of 5637 cells under serum-free conditions.


Signal transduction of fertilization in frog eggs and anti-apoptotic mechanism in human cancer cells: common and specific functions of membrane microdomains.

Sato K - Open Biochem J (2008)

Initiation, promotion and progression of carcinogenesis: from benign tumor to malignant tumor. (A) Survival and growth under microenvironment where no supply of energy and nutrient is available. Serum starvation in cell culture may mimic such a microenvironment in vitro. (B) Anti-apoptotic mechanism of cancer cells. Cell become invasive and enter newly formed capillary (induction of angiogenesis). (C) Newly formed capillary supports growth and survival of tumor. Cells travel through bloodstream and undergo metastasis. This scheme is adapted from “ The Bi9ology of Cancer” by R.A. Weinberg (Garland Science, 2007).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570554&req=5

Figure 3: Initiation, promotion and progression of carcinogenesis: from benign tumor to malignant tumor. (A) Survival and growth under microenvironment where no supply of energy and nutrient is available. Serum starvation in cell culture may mimic such a microenvironment in vitro. (B) Anti-apoptotic mechanism of cancer cells. Cell become invasive and enter newly formed capillary (induction of angiogenesis). (C) Newly formed capillary supports growth and survival of tumor. Cells travel through bloodstream and undergo metastasis. This scheme is adapted from “ The Bi9ology of Cancer” by R.A. Weinberg (Garland Science, 2007).
Mentions: There are several experimental conditions that promote apoptosis in cultured cancer cells. They include application of Fas ligand, a death inducer, or anti-Fas antibody, hypoxia, hydrogen peroxide, irradiation, and chemical inhibitors for metabolic enzymes or signaling pathways etc. [87-89]. Serum starvation serves as one of such pro-apoptotic cellular conditions examined to date. At the initial stage of carcinogenesis, cancer cells are not necessarily surrounded by capillary system. Under such microenvironment, however, cancer cells can proliferate effectively; thereby they are capable of inducing angiogenesis that will help cancer cells to populate more and to undergo invasion and metastasis (Fig. 3). We have employed human bladder carcinoma cell line 5637 as a model cell system to analyze molecular mechanism of serum starvation-resistant growth of cancer cells [90-92]. Survival and growth of this cell line in serum-free conditions have been reported to involve the actions of ligands for epidermal growth factor receptor/kinase (EGFR/kinase) [93], suggesting that protein tyrosine phosphorylation plays a central part of survival signaling. In support of this, immunoblotting with anti-phosphotyrosine antibody has demonstrated that a number of proteins become tyrosine-phosphorylated in response to serum starvation [94]. Interestingly, time course of increase in tyrosine phosphorylation is quite slow; about eight hours are required for its plateau phase, indicating that up-regulation of EGFR/kinase ligands, if any, may need some hours to be promoted. Immunoprecipitation studies have demonstrated that 170-kDa EGFR/kinase is tyrosine-phosphorylated in serum-starved 5637 cells; however, it is different from a more prominently tyrosine-phosphorylated protein of 145 kDa. Mass spectrometric analysis has demonstrated that it is β-subunit of hepatocyte growth factor receptor/kinase (HGFR/kinase or c-Met). Although HGFR/kinase and its cognate high affinity ligand HGF/scatter factor (SF) have been originally identified in liver cells (hepatocytes), they are ubiquitously expressed in many kinds of cells and tissues, and implicated in a number of cellular functions (growth, differentiation, apoptosis etc.) [95,96]. Therefore, it is possible to think that, in addition to EGFR/kinase and its ligands, HGFR/kinase and HGF/SF are involved in the survival mechanism of 5637 cells under serum-free conditions.

Bottom Line: Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein.Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus.Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cell and Developmental Biology, Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan. kksato@cc.kyoto-su.ac.jp

ABSTRACT
Membrane microdomains or lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of lipids (e.g. cholesterol, sphingolipids) and proteins (e.g. glycosylphosphatidylinositol-anchored proteins, growth factor receptor/kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein. Protease activity toward uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of uroplakin III seems to be catalyzed by the egg tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called 'egg activation'. Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder carcinoma cells.

No MeSH data available.


Related in: MedlinePlus