Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression
Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression
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DOI：
10.1038/s41598-019-49744-3
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发表时间：
2019-09-13
影响因子：
4.6
通讯作者：
Sasaki, Takehiko
中科院分区：
文献类型：
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作者：
Koizumi, Atsushi;Narita, Shintaro;Sasaki, Takehiko
磷脂酰肌醇(PIP)参与许多细胞过程，包括癌症进展；然而，与前列腺癌(PCa)相关的PIP的代谢特征尚不清楚。我们用质谱仪研究了PTEN缺失的前列腺癌细胞系、前列腺癌患者的前列腺组织和良性前列腺增生症(BPH)标本中的PIPs谱。在永生化的人前列腺PNT1B细胞中，PTEN缺乏增加了磷脂酰肌醇三磷酸(PIP3)，降低了磷脂酰肌醇一磷酸和双磷酸(PIP1和PIN2)，这与PTEN作为PI(3，4，5)P-3 3-磷酸酶的功能一致。前列腺癌组织中总磷脂酰肌醇(PI)和磷脂酰肌醇(PIP1)含量显著高于BPH组织，而PIP2和PIP3含量显著低于BPH组织。PCa患者的PI、PIP1和PIP2的比例显著高于BPH患者，酰链上0-2个双键的比例显著高于BPH患者。在基于PCA侵袭性的亚组分析中，病理T3期患者的酰链0-2双键PI的平均总水平显著高于病理T2期患者。这些数据表明，PIPs水平的改变和酰基链的饱和可能与前列腺癌的发展和侵袭性有关，尽管这种改变是否是原因尚不清楚。
Phosphoinositides (PIPs) participate in many cellular processes, including cancer progression; however, the metabolic features of PIPs associated with prostate cancer (PCa) are unknown. We investigated PIPs profiles in PTEN-deficient prostate cancer cell lines, human prostate tissues obtained from patients with PCa and benign prostate hyperplasia (BPH) specimens using mass spectrometry. In immortalized normal human prostate PNT1B cells, PTEN deficiency increased phosphatidylinositol tris-phosphate (PIP3) and decreased phosphatidylinositol mono- and bis-phosphate (PIP1 and PIN2 consistent with PTEN's functional role as a PI(3,4,5)P-3 3-phosphatase. In human prostate tissues, levels of total (sum of all acyl variants) phosphatidylinositol (PI) and PIP1 in PCa were significantly higher than in BPH, whereas PIP2 and PIP3 contents were significantly lower than in BPH. PCa patients had significantly higher proportion of PI, PIP1, and PIP2 with 0-2 double bonds in acyl chains than BPH patients. In subgroup analyses based on PCa aggressiveness, mean total levels of PI with 0-2 double bonds in acyl chains were significantly higher in patients with pathological stage T3 than in those with pathological stage T2. These data indicate that alteration of PIPs level and the saturation of acyl chains may be associated with the development and aggressiveness of prostate cancer, although it is unknown whether this alteration is causative.