ArticlePloS one2010
Positive feedback regulation between phospholipase D and Wnt signaling promotes Wnt-driven anchorage-independent growth of colorectal cancer cells.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Lipidomic profiling of endometrial cancer using desorption electrospray ionization mass spectrometry imaging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-cell RNA-sequencing and genome-wide Mendelian randomisation along with abundant machine learning methods identify a novel B cells signature in gastric cancer.Discover oncology · 2025Article
- PLD1 is a key player in cancer stemness and chemoresistance: Therapeutic targeting of cross-talk between the PI3K/Akt and Wnt/β-catenin pathways.Experimental & molecular medicine · 2024Review
- Wnt3a is a promising target in colorectal cancer.Medical oncology (Northwood, London, England) · 2023Review
- MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets.International journal of molecular sciences · 2022Review
- Cancer-associated stroma reveals prognostic biomarkers and novel insights into the tumour microenvironment of colorectal cancer and colorectal liver metastases.Cancer medicine · 2022Article
- Identification and Characterization of the Roles of circCASP9 in Gastric Cancer Based on a circRNA-miRNA-mRNA Regulatory Network.Oxidative medicine and cellular longevity · 2022Article
- Click chemistry-enabled CRISPR screening reveals GSK3 as a regulator of PLD signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of Colon Cancer Cells through Activating NF- κ Bp65 Signaling Pathway.Pathology oncology research : POR · 2020Article
- Emerging Roles of Wnt Ligands in Human Colorectal Cancer.Frontiers in oncology · 2020Review
- Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment.Oncogene · 2019Article
- MicroRNA-766-3p Inhibits Tumour Progression by Targeting Wnt3a in Hepatocellular Carcinoma.Molecules and cells · 2018Article
- Detecting Disease Specific Pathway Substructures through an Integrated Systems Biology Approach.Non-coding RNA · 2017Article
- Inhibition of phospholipaseD2 increases hypoxia-induced human colon cancer cell apoptosis through inactivating of the PI3K/AKT signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Positive feedback loop of hepatoma-derived growth factor and β-catenin promotes carcinogenesis of colorectal cancer.Oncotarget · 2015Article
- Wnt3a: functions and implications in cancer.Chinese journal of cancer · 2015Review
- A dynamic exchange of TCF3 and TCF4 transcription factors controls MYC expression in colorectal cancer cells.Cell cycle (Georgetown, Tex.) · 2015Article
- Hypoxia-inducible factor 1-alpha up-regulates the expression of phospholipase D2 in colon cancer cells under hypoxic conditions.Medical oncology (Northwood, London, England) · 2015Article
- A river runs through it: how autophagy, senescence, and phagocytosis could be linked to phospholipase D by Wnt signaling.Journal of leukocyte biology · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant activation of the canonical Wnt/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Phopholipase D (PLD) has been implicated in progression of colorectal carcinoma However, an understanding of the targets and regulation of this important pathway remains incomplete and besides, relationship between Wnt signaling and PLD is not known. METHODOLOGY/PRINCIPAL
findingsHere, we demonstrate that PLD isozymes, PLD1 and PLD2 are direct targets and positive feedback regulators of the Wnt/beta-catenin signaling. Wnt3a and Wnt mimetics significantly enhanced the expression of PLDs at a transcriptional level in HCT116 colorectal cancer cells, whereas silencing of beta-catenin gene expression or utilization of a dominant negative form of T cell factor-4 (TCF-4) inhibited expression of PLDs. Moreover, both PLD1 and PLD2 were highly induced in colon, liver and stomach tissues of mice after injection of LiCl, a Wnt mimetic. Wnt3a stimulated formation of the beta-catenin/TCF complexes to two functional TCF-4-binding elements within the PLD2 promoter as assessed by chromatin immunoprecipitation assay. Suppressing PLD using gene silencing or selective inhibitor blocked the ability of beta-catenin to transcriptionally activate PLD and other Wnt target genes by preventing formation of the beta-catenin/TCF-4 complex, whereas tactics to elevate intracellular levels of phosphatidic acid, the product of PLD activity, enhanced these effects. Here we show that PLD is necessary for Wnt3a-driven invasion and anchorage-independent growth of colon cancer cells. CONCLUSION/SIGNIFICANCE: PLD isozyme acts as a novel transcriptional target and positive feedback regulator of Wnt signaling, and then promotes Wnt-driven anchorage-independent growth of colorectal cancer cells. We propose that therapeutic interventions targeting PLD may confer a clinical benefit in Wnt/beta-catenin-driven malignancies.
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