GROα overexpression drives cell migration and invasion in triple negative breast cancer cells.
GROα overexpression drives cell migration and invasion in triple negative breast cancer cells.
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DOI：
10.3892/or.2017.5668
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发表时间：
2017-07
期刊：
影响因子：
4.2
通讯作者：
Vadgama JV
中科院分区：
文献类型：
--
作者：
Bhat K;Sarkissyan M;Wu Y;Vadgama JV
三阴性乳腺癌（TNBC）是一种预后不良的高度侵袭性乳腺癌亚型。TNBC的主要特征性特征是其缺乏作为治疗靶标的ER、PR和HER 2受体的表达。因此，必须确定靶向TNBC的新治疗策略。我们的目的是检查GROα是否是TNBC转移的特异性标志物。为此，我们进行了qPCR、ELISA、迁移/侵袭测定、蛋白质印迹和siRNA转染。对不同乳腺癌（BC）亚型中基线GROα表达的评估显示，其在乳腺肿瘤细胞中显著上调，特别是在TNBC细胞系中。在对另外17个TNBC细胞系的进一步评估中，我们发现在>50%的细胞系中基线GROα表达显著升高，从而验证了GROα过表达，特别是在TNBC细胞中。此外，GROα刺激MCF 7和SKBR 3细胞以及GROα敲低MDA-MB-231和HCC 1937细胞引起体外迁移和侵袭能力的显著变化。在表型修饰的BC细胞中也观察到EMT标志物的相应变化。此外，GROα通过MAPK途径调节EMT标志物和迁移/侵袭，PD 98059特异性抑制GROα对BC细胞的作用，可逆转GROα对BC细胞的作用。总之，我们的研究提供了强有力的证据表明GROα是TNBC迁移/侵袭的关键调节剂，并提出GROα作为治疗TNBC转移的潜在治疗靶点。
Triple negative breast cancer (TNBC) is a subtype of highly aggressive breast cancer with poor prognosis. The main characteristic feature of TNBC is its lack of expression of ER, PR and HER2 receptors that are targets for treatments. Hence, it is imperative to identify novel therapeutic strategies to target TNBC. Our aim was to examine whether GROα is a specific marker for TNBC metastasis. For this we performed qPCR, ELISA, migration/invasion assays, western blotting, and siRNA transfections. Evaluation of baseline GROα expression in different breast cancer (BC) subtypes showed that it is significantly upregulated in breast tumor cells, specifically in TNBC cell line. On further evaluation in additional 17 TNBC cell lines we found that baseline GROα expression was significantly elevated in >50% of the cell lines validating GROα overexpression specifically in TNBC cells. Moreover, GROα-stimulation in MCF7 and SKBR3 cells and GROα-knockdown in MDA-MB-231 and HCC1937 cells elicited dramatic changes in migration and invasion abilities in vitro. Corresponding changes in EMT markers were also observed in phenotypically modified BC cells. Furthermore, mechanistic studies identified GROα regulating EMT markers and migration/invasion via MAPK pathway and specific inhibition using PD98059 resulted in the reversal of effects induced by GROα on BC cells. In conclusion, our study provides strong evidence to suggest that GROα is a critical modulator of TNBC migration/invasion and proposes GROα as a potential therapeutic target for treatment of TNBC metastasis.