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Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene.

Publication ,  Journal Article
Ganesan, K; Ivanova, T; Wu, Y; Rajasegaran, V; Wu, J; Lee, MH; Yu, K; Rha, SY; Chung, HC; Ylstra, B; Meijer, G; Lian, KO; Grabsch, H; Tan, P
Published in: Cancer Res
June 1, 2008

Elevated expression of the PLA2G2A phospholipase in gastric cancer (GC) is associated with improved patient survival. To elucidate function and regulation of PLA2G2A in GC, we analyzed a panel of GC cell lines. PLA2G2A was specifically expressed in lines with constitutive Wnt activity, implicating beta-catenin-dependent Wnt signaling as a major upstream regulator of PLA2G2A expression. The invasive ability of PLA2G2A-expressing AGS cells was enhanced by PLA2G2A silencing, whereas cellular migration in non-PLA2G2A-expressing N87 cells was inhibited by enforced PLA2G2A expression, indicating that PLA2G2A is both necessary and sufficient to function as an inhibitor of GC invasion in vitro. We provide evidence that antiinvasive effect of PLA2G2A occurs, at least in part, through its ability to inhibit the S100A4 metastasis mediator gene. Consistent with its invasion inhibitor role, PLA2G2A expression was elevated in primary gastric, colon, and prostrate early-stage tumors, but was decreased in metastatic and late-stage tumors. There was a strong association between PLA2G2A promoter methylation status and PLA2G2A expression, suggesting that the loss of PLA2G2A expression in late-stage cancers may be due to epigenetic silencing. Supporting this, among the non-PLA2G2A-expressing lines, pharmacologic inhibition of epigenetic silencing reactivated PLA2G2A in Wnt-active lines, but in non-Wnt-active lines, a combination of Wnt hyperactivation and inhibition of epigenetic silencing were both required for PLA2G2A reactivation. Our results highlight the complexity of PLA2G2A regulation and provide functional evidence for PLA2G2A as an important regulator of invasion and metastasis in GC.

Duke Scholars

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 1, 2008

Volume

68

Issue

11

Start / End Page

4277 / 4286

Location

United States

Related Subject Headings

  • beta Catenin
  • Wnt Proteins
  • TCF Transcription Factors
  • Stomach Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Humans
 

Citation

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ICMJE
MLA
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Ganesan, K., Ivanova, T., Wu, Y., Rajasegaran, V., Wu, J., Lee, M. H., … Tan, P. (2008). Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene. Cancer Res, 68(11), 4277–4286. https://doi.org/10.1158/0008-5472.CAN-07-6517
Ganesan, Kumaresan, Tatiana Ivanova, Yonghui Wu, Vikneswari Rajasegaran, Jeanie Wu, Ming Hui Lee, Kun Yu, et al. “Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene.Cancer Res 68, no. 11 (June 1, 2008): 4277–86. https://doi.org/10.1158/0008-5472.CAN-07-6517.
Ganesan K, Ivanova T, Wu Y, Rajasegaran V, Wu J, Lee MH, et al. Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene. Cancer Res. 2008 Jun 1;68(11):4277–86.
Ganesan, Kumaresan, et al. “Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene.Cancer Res, vol. 68, no. 11, June 2008, pp. 4277–86. Pubmed, doi:10.1158/0008-5472.CAN-07-6517.
Ganesan K, Ivanova T, Wu Y, Rajasegaran V, Wu J, Lee MH, Yu K, Rha SY, Chung HC, Ylstra B, Meijer G, Lian KO, Grabsch H, Tan P. Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene. Cancer Res. 2008 Jun 1;68(11):4277–4286.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 1, 2008

Volume

68

Issue

11

Start / End Page

4277 / 4286

Location

United States

Related Subject Headings

  • beta Catenin
  • Wnt Proteins
  • TCF Transcription Factors
  • Stomach Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Humans