Pyruvate Carboxylase Is Up-Regulated in Breast Cancer and Essential to Support Growth and Invasion of MDA-MB-231 Cells.
Pyruvate Carboxylase Is Up-Regulated in Breast Cancer and Essential to Support Growth and Invasion of MDA-MB-231 Cells.
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DOI：
10.1371/journal.pone.0129848
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Jitrapakdee S
中科院分区：
文献类型：
--
作者：
Phannasil P;Thuwajit C;Warnnissorn M;Wallace JC;MacDonald MJ;Jitrapakdee S
丙酮酸羧化酶（PC）是催化丙酮酸羧化为草酰乙酸的回补酶，当三羧酸循环中间体用于生物合成目的时，这对于补充三羧酸循环中间体至关重要。我们通过免疫组化检测了57例乳腺癌患者不同阶段的石蜡包埋乳腺组织切片中PC的表达。PC在乳腺癌组织中的表达水平高于非癌组织。我们还发现PC表达水平与肿瘤大小和肿瘤分期之间存在统计学相关性（P < 0.05）。在具有不同转移潜能的四种乳腺癌细胞系中进一步研究了PC与这两个参数的关系;即，MCF-7、SKBR 3（低转移）、MDA-MB-435（中度转移）和MDA-MB-231（高转移）。MDA-MB-231和MDA-MB-435细胞中PC mRNA和蛋白的丰度比MCF-7和SKBR 3细胞高2-3倍。siRNA介导的MDA-MB-231和MDA-MB-435细胞中PC表达的敲低导致细胞增殖、迁移和体外侵袭能力在谷氨酰胺依赖和谷氨酰胺耗尽条件下降低50%。PC在MCF-7细胞中的过表达导致其增殖率、迁移和侵袭能力增加2倍。综上所述，上述结果表明，通过PC回补对于乳腺癌细胞支持其生长和运动是重要的。
Pyruvate carboxylase (PC) is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P < 0.05). The involvement of PC with these two parameters was further studied in four breast cancer cell lines with different metastatic potentials; i.e., MCF-7, SKBR3 (low metastasis), MDA-MB-435 (moderate metastasis) and MDA-MB-231 (high metastasis). The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.
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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：
4.8
作者：
Lu, Xin;Bennet, Bryson;Kang, Yibin
通讯作者：
Kang, Yibin
具有IDH1突变的胶质瘤细胞通过丙酮酸羧化酶调节代谢分数通量。
影响因子：
3.7
作者：
Izquierdo-Garcia JL;Cai LM;Chaumeil MM;Eriksson P;Robinson AE;Pieper RO;Phillips JJ;Ronen SM
通讯作者：
Ronen SM
影响因子：
29
作者：
Marin-Valencia I;Yang C;Mashimo T;Cho S;Baek H;Yang XL;Rajagopalan KN;Maddie M;Vemireddy V;Zhao Z;Cai L;Good L;Tu BP;Hatanpaa KJ;Mickey BE;Matés JM;Pascual JM;Maher EA;Malloy CR;Deberardinis RJ;Bachoo RM
通讯作者：
Bachoo RM
影响因子：
37.3
作者：
Fan TW;Lane AN;Higashi RM;Farag MA;Gao H;Bousamra M;Miller DM
通讯作者：
Miller DM