Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer

Uehara, Takashi; Kikuchi, Hirotoshi; Miyazaki, Shôzo; Iino, Ichirota; Setoguchi, Tomohiko; Hiramatsu, Yoshihiro; Ohta, Michio; Kamiya, Kinji; Morita, Yoshifumi; Tanaka, Hiroki; Baba, Satoshi; Hayasaka, Takahiro; Setou, Mitsutoshi; Konno, Hiroyuki

doi:10.1245/s10434-015-4459-6

Cited by 95 publications

(81 citation statements)

References 34 publications

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“…The lower levels of LysoPCs may reflect a higher metabolism rate in cancer patients. LysoPC is an important intermediate in the degradation and biosynthesis of phosphatidylcholine (PC) which has been an important biomarker in cancer diagnosis, such as breast cancer22, lung cancer23, ovarian cancer2425, gastric cancer26, colorectal cancer27 and melanoma28. LysoPC levels were shown to be decreased in the serum or urine of these cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…LysoPCs can be an important precursor for the synthesis of PC by the action of LPCAT1 which is overexpressed in several cancers, and increased incorporation of PCs into cell membranes may facilitate the proliferation, adhesion, and motility of cancer cells2630. LPCAT1 has been an independent predictor of early tumor recurrence and represents a novel prognostic biomarker for breast cancer, gastric cancer and prostate cancer263132.…”

Section: Discussionmentioning

confidence: 99%

“…LPCAT1 has been an independent predictor of early tumor recurrence and represents a novel prognostic biomarker for breast cancer, gastric cancer and prostate cancer263132. LysoPCs are also a substrate of lysophospholipase D (lysoPLD)3334.…”

Section: Discussionmentioning

confidence: 99%

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Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Bao

Liu

Zhang

et al. 2016

Sci Rep

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Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Bao

Liu

Zhang

et al. 2016

Sci Rep

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“…Levels of LPCAT1 were higher in gastric cancer tissue than in adjacent non-neoplastic mucosa, and this overexpression was predominant in differentiated adenocarcinomas, so LPCAT1 could play important roles in the tumorigenesis of differentiated adenocarcinomas compared to undifferentiated ones. Moreover, LPCAT1 expression levels were positively correlated with tumor differentiation and negatively with lymph node metastasis, tumor stage and tumor depth, assuming a potential prognostic value [97]. Using two gastric cancer cell lines, Shida et al investigated whether sphingosine 1-phosphate (S1P) induces phosphorylation of two receptors tyrosine kinases (RTKs), such as epidermal growth factor-1 receptor (EGFR) and c-Met, whose signals are crucial in gastric cancer progression.…”

Section: Lipidomics In Cancer Researchmentioning

confidence: 99%

Advances in Lipidomics for Cancer Biomarkers Discovery

Perrotti

Rosa

Cicalini

et al. 2016

IJMS

161

126

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Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy.

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“…In line with these results Uehara et al. found LPCAT 1 overexpression and related lipid alterations in gastric cancer . MSI of colorectal cancer biopsies identified molecular signatures discriminating between healthy and cancerous tissue.…”

Section: Applications Of Msi In the Understanding Of Pathogenesismentioning

confidence: 54%

MALDI mass spectrometry imaging: A cutting‐edge tool for fundamental and clinical histopathology

Longuespée

Casadonte²,

Kriegsmann

et al. 2016

Proteomics Clinical Apps

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Histopathological diagnoses have been done in the last century based on hematoxylin and eosin staining. These methods were complemented by histochemistry, electron microscopy, immunohistochemistry (IHC), and molecular techniques. Mass spectrometry (MS) methods allow the thorough examination of various biocompounds in extracts and tissue sections. Today, mass spectrometry imaging (MSI), and especially matrix-assisted laser desorption ionization (MALDI) imaging links classical histology and molecular analyses. Direct mapping is a major advantage of the combination of molecular profiling and imaging. MSI can be considered as a cutting edge approach for molecular detection of proteins, peptides, carbohydrates, lipids, and small molecules in tissues. This review covers the detection of various biomolecules in histopathological sections by MSI. Proteomic methods will be introduced into clinical histopathology within the next few years.

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Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer

Abstract: Overexpressed LPCAT1 protein in gastric mucosa appears to play important roles in the tumorigenic process of gastric cancer by converting LPC to PC.

Cited by 95 publications

References 34 publications

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Advances in Lipidomics for Cancer Biomarkers Discovery

MALDI mass spectrometry imaging: A cutting‐edge tool for fundamental and clinical histopathology

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