Increased Activity and Intranuclear Expression of Phospholipase D2 in Human Renal Cancer

Zhao, Yutong; Ehara, Hidetoshi; Akao, Yukihiro; Shamoto, Masayo; Nakagawa, Yoshihito; Banno, Yoshiko; Deguchi, Takashi; Ohishi, Nobuko; Yagi, Kunio; Nozawa, Yoshinori

doi:10.1006/bbrc.2000.3719

Cited by 131 publications

(111 citation statements)

References 23 publications

(15 reference statements)

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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%

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%

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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“…61 Phospholipase D overexpression has been reported for many cancer types including breast cancer cell lines and tissue samples, as well as renal and gastric cancers and is associated with mTOR-mediated pro-survival phenotypes. [62][63][64][65] Thus, modification of the intracellular phospholipid code by changes in the expression and/or activity of various phospholipid modifiers can ultimately regulate tumor progression.…”

Section: Alteration Of the Phospholipid Code During Tumor Progressionmentioning

confidence: 99%

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

2015

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A significant effort is made by the cell to maintain certain phospholipids at specific sites. It is well described that proteins involved in intracellular signaling can be targeted to the plasma membrane and organelles through phospholipid-binding domains. Thus, the accumulation of a specific combination of phospholipids, denoted here as the 'phospholipid code', is key in initiating cellular processes. Interestingly, a variety of extracellular proteins and pathogen-derived proteins can also recognize or modify phospholipids to facilitate the recognition of dying cells, tumorigenesis and host-microbe interactions. In this article, we discuss the importance of the phospholipid code in a range of physiological and pathological processes.

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“…PLD activity and expression has been reported to be elevated in a majority of breast (Noh et al, 2000) and renal (Zhao et al, 2000) cancers that were examined. MDA-MB-231 breast cancer cells have very highly elevated levels of PLD activity relative to other breast cancer cells, and PLD activity was implicated in the survival of this breast cancer cell line subjected to apoptotic stress (Zhong et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Alternative phospholipase D/mTOR survival signal in human breast cancer cells

2004

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Increased Activity and Intranuclear Expression of Phospholipase D2 in Human Renal Cancer

Cited by 131 publications

References 23 publications

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

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

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

Alternative phospholipase D/mTOR survival signal in human breast cancer cells

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