Bleb Formation in Human Fibrosarcoma HT1080 Cancer Cell Line Is Positively Regulated by the Lipid Signalling Phospholipase D2 (PLD2)

Achievements in the Life Sciences Pub Date : 2016-12-01 DOI:10.1016/j.als.2016.11.001

Godwin A. Ponuwei, Phil R. Dash

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引用次数: 2

Abstract

Blebs are spherical plasma membrane protrusions formed when the membrane detaches from the underlying cortex as a result of actomyosin contractility-powered increase of hydrostatic pressure in the cytoplasm. Different tumour cells metastasize using blebbing as alternative mode of migration by squeezing through pre-existing pores in the extracellular matrix (ECM). This study investigated the role of the lipid signalling phospholipases D1 and D2 (PLD1/PLD2) in bleb formation in human fibrosarcoma HT1080 cell line in the extracellular matrix, and reports that pharmacological inhibition of PLD1 and PLD2 with a potent universal PLD inhibitor potently inhibited bleb formation in HT1080 cells embedded in three-dimensional (3D) matrigel matrix. Use of smartpool small interfering RNAs (siRNAs) that target PLD1 and PLD2 isoforms at four different sequences revealed that PLD2, but not PLD1 is involved in blebbing of HT1080 cells. Furthermore, we demonstrate that PLD2-mediated bleb formation is via the PA-LPAR-Rho-ROCK signalling pathway. Thus, PLD2 is a promising therapeutic target in combating metastasis of cancers of fibrous connective tissues.

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脂质信号磷脂酶D2 (PLD2)对人纤维肉瘤HT1080癌细胞泡形成的正向调控

气泡是由于肌动球蛋白收缩力引起的细胞质静水压力增加，使细胞膜脱离下层皮层而形成的球形质膜突出物。不同的肿瘤细胞通过挤压细胞外基质(ECM)中预先存在的孔隙，利用起泡作为迁移的替代模式转移。本研究探讨了脂质信号磷脂酶D1和D2 (PLD1/PLD2)在人纤维肉瘤HT1080细胞系细胞外基质中泡形成中的作用，并报道了一种有效的通用PLD抑制剂对PLD1和PLD2的药理抑制能有效抑制HT1080细胞中嵌入三维(3D)基质的泡形成。使用靶向PLD1和PLD2亚型的四种不同序列的smartpool小干扰rna (sirna)发现，PLD2而非PLD1参与HT1080细胞的起泡。此外，我们证明pld2介导的泡形成是通过PA-LPAR-Rho-ROCK信号通路进行的。因此，PLD2是对抗纤维结缔组织癌转移的一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Achievements in the Life Sciences

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