Expression of phospholipase D2 in human colorectal carcinoma

Saito, Masaru; Iwadate, Manabu; Higashimoto, Masashi; Ono, Koichiro; Takebayashi, Yuji; Takenoshita, Seiichi

doi:10.3892/or.18.5.1329

Cited by 42 publications

(49 citation statements)

References 22 publications

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“…Participation of PLD-generated PA in downstream signal transduction from mitogenic growth factor receptors via Ras and the MAP kinase pathway has been demonstrated. 12 In comparison with adjacent non-neoplastic tissues, elevated expression and activity of PLD have been detected in various human tumors, including those of breast, 7,31 colorectal, 32,33 gastric, 34 renal 35 and papillary thyroid cancers. 36 Recent clinical studies have reported on correlation of PLD expression levels with tumor size; an association with survival of patients with colorectal carcinoma was also reported.…”

Section: Discussionmentioning

confidence: 99%

“…36 Recent clinical studies have reported on correlation of PLD expression levels with tumor size; an association with survival of patients with colorectal carcinoma was also reported. 32 A sustained and increased level of PLD can be deleterious and can contribute to the development of cancer. 37 Because of its important role in progression of cancer, PLD could be a target for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

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Autoregulation of phospholipase D activity is coupled to selective induction of phospholipase D1 expression to promote invasion of breast cancer cells

Kang

Park

Kim

et al. 2010

Intl Journal of Cancer

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Phospholipase D (PLD) is an important signaling enzyme implicated in the control of many biological processes, including cell proliferation and survival. Despite the importance of the duration and amplitude of PLD signaling in carcinogenesis, mechanisms that regulate PLD expression remain poorly understood. In our study, we define the regulatory components of the machinery that specifies selective PLD1 induction via signals propagated through PLD activity. We demonstrate for the first time that establishment of a positive feedback loop that is dependent on enzymatic activity originating from both PLD1 and PLD2 isozymes enhances selective expression of PLD1, but not PLD2. Phosphatidic acid, the product of PLD activity, leads to an increase in the Ras-ERK/PI3K-NFjB signaling cascade and enhances binding of NFjB to the PLD1 promoter, consequently inducing selective PLD1 expression in SK-BR3 breast cancer cells. Moreover, selective PLD inhibitor suppressed epidermal growth factor-induced matrix metalloproteinase upregulation and invasion by inhibiting PLD1 expression. In conclusion, we propose that autoregulation of PLD activity might be coupled to induction of PLD1 expression, and thereby play a role in carcinogenesis.Phosphatidic acid (PA) has emerged as an important mediator of lipid signaling that is associated with regulation of cell growth and proliferation, membrane trafficking and cytoskeletal reorganization. Because of its regulatory role, the level of PA itself should be tightly regulated through synthesis and turnover. PA is the product of phosphatidylcholine hydrolysis catalyzed by phospholipase D (PLD) and is strategically located at the intersection of several major signaling and metabolic pathways. Endogenous levels of PA are low in resting cells, and PLD activity is tightly regulated by mechanisms that control secretion, migration, survival and proliferation of cells. 1,2 PLD is activated by a variety of mitogens, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and interleukin 1b (IL-1b), [3][4][5][6][7] and its involvement in many cellular biological processes, including cell proliferation, survival, vesicular trafficking and secretion, has been demonstrated. 1,8 Two distinct isoforms of mammalian PLD, PLD1 and PLD2, have been identified. 9 PLD mediates the parallel reactions of phospholipid hydrolysis and transphosphatidylation. Primary alcohols, such as ethanol or 1-butanol, serve as competitive nucleophiles to water, resulting in a transphosphatidylation reaction that produces a phosphatidylalcohol, such as phosphatidylbutanol (PtdBut), instead of PA. Thus, primary alcohols have been used almost exclusively as the only means of preventing PA production for study of the role of PLD-mediated PA formation in certain cellular processes. 10 Potent dual PLD1 and PLD2 inhibitors, as well as isoformselective PLD inhibitors, with considerable pharmacological characterization have recently been developed. 11 Recent work has demonstrated a novel PA target in the Ras/Raf/ERK si...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Autoregulation of phospholipase D activity is coupled to selective induction of phospholipase D1 expression to promote invasion of breast cancer cells

Kang

Park

Kim

et al. 2010

Intl Journal of Cancer

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“…Overexpression and elevated activity of PLD result in cellular transformation and has been implicated in multiple human cancers including colorectal (Saito et al, 2007;Kang et al, 2008), breast (Noh et al, 2000), renal (Zhao et al, 2000), gastric carcinoma (Uchida et al, 1999), and thyroid cancers . Stable cells overexpressing PLD1 and PLD2 demonstrate anchorage-independent growth and tumorigenesis in nude mice (Min et al, 2001;Buchanan et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells

Kang

Lee

et al. 2009

Exp Mol Med

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In spite of the importance of phospholipase D (PLD) in cell proliferation and tumorigenesis, little is known about the molecules regulating PLD expression. Thus, identification of small molecules inhibiting PLD expression would be an important advance for PLDmediated physiology. We examined one such here, denoted "Triptolide", which was identified in a chemical screen for inhibitors of PLD expression using cell assay system based on measurement of PLD promoter activity.

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“…As discussed above in cell growth signaling, PLD2 and PA can both directly affect mTor signaling, which is a main target of anti-cancer drugs, for example, rapamycin (a competitor of PA) is being used for tumor treatment. In addition, the expression level and activity of PLD2 have been reported to be elevated in several cancers, including colorectal cancer and renal cancer (Zhao et al, 2000;Saito et al, 2007), and to be associated with tumor size and survival (Saito et al, 2007). Furthermore, a PLD2 polymorphism detected in colorectal cancer was found to be closely linked to the prevalence of the disease (Wood et al, 2007).…”

Section: Notementioning

confidence: 96%

“…Vessel occlusioninduced hypoxia in the hippocampus has been reported to increase PLD2 levels (Min do et al, 2007). Furthermore, the expression of PLD2 is known to be significantly elevated in many cancers, including breast, renal, and colon cancer (Zhao et al, 2000;Saito et al, 2007;Wood et al, 2007).…”

Section: Expressionmentioning

confidence: 99%