Phospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer

X. T. Hu, F. B. Zhang, Y. C. Fan, X. S. Shu, A. H.Y. Wong, W. Zhou, Q. L. Shi, H. M. Tang, L. Fu, X. Y. Guan, SunYoung Rha, Q. Tao, C. He

Research output: Contribution to journalArticle

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Abstract

Located at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2′-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis.

Original languageEnglish
Pages (from-to)2466-2475
Number of pages10
JournalOncogene
Volume28
Issue number26
DOIs
Publication statusPublished - 2009 Jul 2

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Phospholipases
Cytoskeleton
Epigenomics
Stomach Neoplasms
Methylation
Neoplasms
Stomach
CpG Islands
decitabine
Down-Regulation
Actin Depolymerizing Factors
Gastric Mucosa
Energy Metabolism
Carcinogenesis
Homeostasis
Phosphorylation
Pharmacology
Calcium
Carcinoma
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Hu, X. T. ; Zhang, F. B. ; Fan, Y. C. ; Shu, X. S. ; Wong, A. H.Y. ; Zhou, W. ; Shi, Q. L. ; Tang, H. M. ; Fu, L. ; Guan, X. Y. ; Rha, SunYoung ; Tao, Q. ; He, C. / Phospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer. In: Oncogene. 2009 ; Vol. 28, No. 26. pp. 2466-2475.
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abstract = "Located at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84{\%} (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62{\%} (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2′-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis.",
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Hu, XT, Zhang, FB, Fan, YC, Shu, XS, Wong, AHY, Zhou, W, Shi, QL, Tang, HM, Fu, L, Guan, XY, Rha, S, Tao, Q & He, C 2009, 'Phospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer', Oncogene, vol. 28, no. 26, pp. 2466-2475. https://doi.org/10.1038/onc.2009.92

Phospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer. / Hu, X. T.; Zhang, F. B.; Fan, Y. C.; Shu, X. S.; Wong, A. H.Y.; Zhou, W.; Shi, Q. L.; Tang, H. M.; Fu, L.; Guan, X. Y.; Rha, SunYoung; Tao, Q.; He, C.

In: Oncogene, Vol. 28, No. 26, 02.07.2009, p. 2466-2475.

Research output: Contribution to journalArticle

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T1 - Phospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer

AU - Hu, X. T.

AU - Zhang, F. B.

AU - Fan, Y. C.

AU - Shu, X. S.

AU - Wong, A. H.Y.

AU - Zhou, W.

AU - Shi, Q. L.

AU - Tang, H. M.

AU - Fu, L.

AU - Guan, X. Y.

AU - Rha, SunYoung

AU - Tao, Q.

AU - He, C.

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AB - Located at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2′-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis.

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