Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis
Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis
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DOI：
10.1016/j.job.2020.07.001
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发表时间：
2020-09-01
影响因子：
2.4
通讯作者：
Kubota, Satoshi
中科院分区：
文献类型：
--
作者：
Akashi, Sho;Nishida, Takashi;Kubota, Satoshi
目的：乳腺癌的抗破骨治疗偶尔会引起药物相关性颌骨坏死。此外，在这些乳腺癌细胞中通常观察到糖酵解活性升高，即所谓的Warburg效应。之前，我们发现细胞通信网络因子2 （CCN2）的产生和糖酵解在软骨细胞中相互增强。在这里，我们评估了CCN2与乳腺癌细胞糖酵解之间的相互作用，因为我们怀疑CCN2可能参与了高度侵袭性乳腺癌细胞的Warburg效应。方法：采用两种具有不同表型的人乳腺癌细胞系。使用2种不同的化合物抑制糖酵解，并使用siRNA进行基因沉默。分别通过比色法和定量RT-PCR检测糖酵解和相关基因的表达。结果：虽然用siRNA鸡尾酒靶向CCN2治疗浸润性乳腺癌细胞时，CCN2表达几乎完全沉默，但糖酵解活性不受影响。值得注意的是，在乳腺癌细胞中，糖酵解酶基因的表达在CCN2沉默后趋于增加，而糖酵解酶基因在软骨细胞中因CCN2缺乏而受到抑制。糖酵解的抑制导致软骨细胞中CCN2表达的抑制，但在浸润性和非浸润性乳腺癌细胞中分别没有改变或强烈增强CCN2表达。结论：CCN2高表达水平在乳腺癌的侵袭转移过程中起关键作用。因此，糖酵解导致CCN2内在抑制机制的崩溃可能会诱导乳腺癌细胞获得侵袭性表型。(C) 2020日本口腔生物学协会。Elsevier B.V.版权所有。
Objectives: Anti-osteoclastic treatments for breast cancer occasionally cause medication-related osteonecrosis of the jaw. Moreover, elevated glycolytic activity, which is known as the Warburg effect, is usually observed in these breast cancer cells. Previously, we found that cellular communication network factor 2 (CCN2) production and glycolysis enhanced each other in chondrocytes. Here, we evaluated the interplay between CCN2 and glycolysis in breast cancer cells, as we suspected a possible involvement of CCN2 in the Warburg effect in highly invasive breast cancer cells.Methods: Two human breast cancer cell lines with a distinct phenotype were used. Glycolysis was inhibited by using 2 distinct compounds, and gene silencing was performed using siRNA. Glycolysis and the expression of relevant genes were monitored via colorimetric assays and quantitative RT-PCR, respectively.Results: Although CCN2 expression was almost completely silenced when treating invasive breast cancer cells with a siRNA cocktail against CCN2, glycolytic activity was not affected. Notably, the expression of glycolytic enzyme genes, which was repressed by CCN2 deficiency in chondrocytes, tended to increase upon CCN2 silencing in breast cancer cells. Inhibition of glycolysis, which resulted in the repression of CCN2 expression in chondrocytic cells, did not alter or strongly enhanced CCN2 expression in the invasive and non-invasive breast cancer cells, respectively.Conclusions: High CCN2 expression levels play a critical role in the invasion and metastasis of breast cancer. Thus, a collapse in the intrinsic repressive machinery of CCN2 due to glycolysis may induce the acquisition of an invasive phenotype in breast cancer cells. (C) 2020 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.