Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation, migration, and invasion.
Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation, migration, and invasion.
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DOI：
10.1002/nbm.3573
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发表时间：
2016-08
影响因子：
2.9
通讯作者：
Glunde K
中科院分区：
文献类型：
--
作者：
Cao MD;Cheng M;Rizwan A;Jiang L;Krishnamachary B;Bhujwalla ZM;Bathen TF;Glunde K
胆碱磷脂代谢异常与肿瘤发生和肿瘤进展有关。我们研究了靶向胆碱磷脂代谢的影响，沉默两个甘油磷酸二酯酶基因，GDPD 5和GDPD 6，使用小干扰RNA（siRNA）在两个乳腺癌细胞系，MCF-7和MDA-MB-231。GDPD 5和GDPD 6 siRNA治疗导致甘油磷酸胆碱（GPC）水平显着增加，而磷酸胆碱（PC）和游离胆碱水平没有变化，这进一步支持了它们作为GPC特异性调节剂在乳腺癌中的作用。GPC水平在GDPD 6沉默期间增加超过两倍，并且在GDPD 5沉默期间略微增加。在用GDPD 5和GDPD 6 siRNA处理的两种细胞系中DNA梯状化均为阴性，表明不存在细胞凋亡。用GDPD 5 siRNA处理在72小时引起两种乳腺癌细胞系中的细胞增殖降低，而GDPD 6 siRNA处理在72小时降低MCF-7中的细胞增殖，但在MDA-MB-231细胞中不降低。在用GDPD 5或GDPD 6 siRNA处理的MDA-MB-231细胞中观察到细胞迁移和侵袭减少，其中与GDPD 6 siRNA处理相比，在GDPD 5 siRNA处理下观察到细胞迁移和侵袭的更显著减少。总之，GDPD 6沉默比GDPD 5沉默更深刻地增加了乳腺癌细胞中的GPC水平，而GDPD 5沉默对细胞增殖、迁移和侵袭的影响比GDPD 6沉默更严重。我们的研究结果表明，沉默GDPD 5和GDPD 6单独或组合可能有潜力作为乳腺癌治疗的新的分子靶向策略。
Abnormal choline phospholipid metabolism is associated with oncogenesis and tumor progression. We have investigated the effects of targeting choline phospholipid metabolism by silencing two glycerophosphodiesterase genes, GDPD5 and GDPD6, using small interfering RNA (siRNA) in two breast cancer cell lines, MCF-7 and MDA-MB-231. Treatment with GDPD5 and GDPD6 siRNA resulted in significant increases in glycerophosphocholine (GPC) levels, and no change in the levels of phosphocholine (PC) and free choline, which further supports their role as GPC specific regulators in breast cancer. The GPC levels were more than twofold increased during GDPD6 silencing, and marginally increased during GDPD5 silencing. DNA laddering was negative in both cell lines treated with GDPD5 and GDPD6 siRNA, indicating absence of apoptosis. Treatment with GDPD5 siRNA caused a decrease in cell proliferation in both breast cancer cell lines at 72h, while GDPD6 siRNA treatment decreased cell proliferation in MCF-7 at 72h, but not in MDA-MB-231 cells. Decreased cell migration and invasion were observed in MDA-MB-231 cells treated with GDPD5 or GDPD6 siRNA, where a more pronounced reduction in cell migration and invasion was observed under GDPD5 siRNA treatment as compared to GDPD6 siRNA treatment. In conclusion, GDPD6 silencing increased the GPC levels in breast cancer cells more profoundly than GDPD5 silencing, while the effects of GDPD5 silencing on cell proliferation, migration, and invasion were more severe than those of GDPD6 silencing. Our results suggest that silencing GDPD5 and GDPD6 alone or in combination may have potential as new molecular targeting strategy for breast cancer treatment.
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DOI：
10.1093/jnci/53.3.661
发表时间：
1974-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
CAILLEAU, R;YOUNG, R;REEVES, WJ
通讯作者：
REEVES, WJ
影响因子：
3.8
作者：
Cao MD;Giskeødegård GF;Bathen TF;Sitter B;Bofin A;Lønning PE;Lundgren S;Gribbestad IS
通讯作者：
Gribbestad IS
影响因子：
11.2
作者：
Krishnamachary B;Glunde K;Wildes F;Mori N;Takagi T;Raman V;Bhujwalla ZM
通讯作者：
Bhujwalla ZM
DOI：
10.1038/nrc3162
发表时间：
2011-11-17
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.9
作者：
Cao, Maria D.;Sitter, Beathe;Gribbestad, Ingrid S.
通讯作者：
Gribbestad, Ingrid S.