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Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models

Abstract : Prostate cancer (PCa) is the most frequent cancer among men and the first cause of death over 65. Approximately 90% of patients with advanced disease will develop bone metastasis, which dramatically reduces long-term survival. Therefore, effective therapies need to be developed, especially when disease is still well-localized. Phospholipase D (PLD), an enzyme that hydrolyzes phosphatidylcholine to yield phosphatidic acid, regulates several cellular functions as proliferation, survival, migration or vesicular trafficking. PLD is implicated in numerous diseases such as neurodegenerative, cardiovascular, autoimmune disorders or cancer. Indeed, PLD controls different aspects of oncogenesis including tumor progression and resistance to targeted therapies such as radiotherapy. PLD1 and PLD2 are the only isoforms with catalytic activity involved in cancer. Surprisingly, studies deciphering the role of PLD in the pathophysiology of PCa are scarce. Here we describe the correlation between PLD activity and PLD1 and PLD2 expression in PCa bone metastasis-derived cell lines C4-2B and PC-3. Next, by using PLD pharmacological inhibitors and RNA interference strategy, we validate the implication of PLD1 and PLD2 in cell viability, clonogenicity and proliferation of C4-2B and PC-3 cells and in migration capacity of PC-3 cells. Last, we show an increase in PLD activity as well as PLD2 protein expression during controlled starvation of PC-3 cells, concomitant with an augmentation of its migration capacity. Specifically, upregulation of PLD activity appears to be PKC-independent. Taken together, our results indicate that PLD, and in particular PLD2, could be considered as a potential therapeutic target for the treatment of PCa-derived bone metastasis.
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https://hal-cnrs.archives-ouvertes.fr/hal-03019019
Contributor : Colette Orange <>
Submitted on : Monday, November 23, 2020 - 11:04:10 AM
Last modification on : Tuesday, November 24, 2020 - 3:21:21 AM

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Mathieu Borel, Olivier Cuvillier, David Magne, Saida Mebarek, Leyre Brizuela. Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models. Molecular and Cellular Biochemistry, Springer Verlag, 2020, 473 (1-2), pp.263-279. ⟨10.1007/s11010-020-03827-2⟩. ⟨hal-03019019⟩

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