The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.
The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.
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DOI：
10.18632/oncotarget.26357
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发表时间：
2018-11-20
期刊：
影响因子：
--
通讯作者：
Storz, Peter
中科院分区：
文献类型：
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作者：
Durand, Nisha;Borges, Sahra;Storz, Peter
磷脂酰肌醇-4-磷酸5-激酶-1C（PIP 5 K1 C）是一种脂质激酶，通过磷脂酰肌醇-4，5-二磷酸（PI 4，5 P2）的位点特异性形成来调节粘着斑动力学和细胞附着。通过比较正常乳腺组织原位癌和浸润性导管癌亚型，我们在这里表明，PIP 5 K1 C在丝氨酸残基448（S448）的磷酸化状态可以预测乳腺癌进展到一个积极的表型，而PIP 5 K1 C的表达水平并不指示这一事件。在浸润性导管癌中，S448处的PIP 5 K1 C磷酸化下调，类似地，PKD 1（在该位点磷酸化PIP 5 K1 C的激酶）的表达水平降低。总体而言，由于PKD 1是乳腺癌细胞迁移和侵袭的负调节因子，因此该残基的磷酸化状态可作为乳腺肿瘤侵袭性的指标。
Phosphatidylinositol-4-phosphate 5-kinase type-1C (PIP5K1C) is a lipid kinase that regulates focal adhesion dynamics and cell attachment through site-specific formation of phosphatidylinositol-4,5-bisphosphate (PI4,5P2). By comparing normal breast tissue to carcinoma in situ and invasive ductal carcinoma subtypes, we here show that the phosphorylation status of PIP5K1C at serine residue 448 (S448) can be predictive for breast cancer progression to an aggressive phenotype, while PIP5K1C expression levels are not indicative for this event. PIP5K1C phosphorylation at S448 is downregulated in invasive ductal carcinoma, and similarly, the expression levels of PKD1, the kinase that phosphorylates PIP5K1C at this site, are decreased. Overall, since PKD1 is a negative regulator of cell migration and invasion in breast cancer, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.