ATG9A Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of Pro-Cancer Phenotypes
ATG9A Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of Pro-Cancer Phenotypes
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DOI：
10.3390/cells7120248
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发表时间：
2018-12-01
期刊：
影响因子：
6
通讯作者：
Hervouet, Eric
中科院分区：
文献类型：
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作者：
Claude-Taupin, Aurore;Fonderflick, Leila;Hervouet, Eric
早期发现和有针对性的治疗已经导致与乳腺癌（BC）相关的死亡率显著下降，然而，未来需要解决一些重要问题。其中之一将是寻找新的三阴性乳腺癌（TNBC）治疗策略，因为目前还没有针对这种亚型的有效治疗策略。由于大量研究报道了靶向自噬途径治疗或限制癌症进展的可能性，我们分析了6个自噬基因（ATG9A、ATG9B、BECLIN1、LC3B、NIX和P62/SQSTM1）在乳腺癌组织中的表达，并将其与健康邻近组织的表达进行了比较。在我们的研究中，我们观察到乳腺癌队列中TNBC样本中ATG9A mRNA表达增加。我们还发现，在石蜡包埋组织的蛋白质水平上，转录本的增加得到了证实。为了证实这些体内数据，我们设计了shRNA-和CRISPR/ cas9驱动的ATG9A在三阴性乳腺癌细胞系MDA-MB-436中的表达抑制，以确定其在调节癌症表型中的作用。我们发现ATG9A抑制导致体外肿瘤特征的抑制，这表明ATG9A可以被认为是TNBC的新标志物，并可能在未来被认为是开发新的特异性TNBC治疗的靶点。
Early detection and targeted treatments have led to a significant decrease in mortality linked to breast cancer (BC), however, important issues need to be addressed in the future. One of them will be to find new triple negative breast cancer (TNBC) therapeutic strategies, since none are currently efficiently targeting this subtype of BC. Since numerous studies have reported the possibility of targeting the autophagy pathway to treat or limit cancer progression, we analyzed the expression of six autophagy genes (ATG9A, ATG9B, BECLIN1, LC3B, NIX and P62/SQSTM1) in breast cancer tissue, and compared their expression with healthy adjacent tissue. In our study, we observed an increase in ATG9A mRNA expression in TNBC samples from our breast cancer cohort. We also showed that this increase of the transcript was confirmed at the protein level on paraffin-embedded tissues. To corroborate these in vivo data, we designed shRNA- and CRISPR/Cas9-driven inhibition of ATG9A expression in the triple negative breast cancer cell line MDA-MB-436, in order to determine its role in the regulation of cancer phenotypes. We found that ATG9A inhibition led to an inhibition of in vitro cancer features, suggesting that ATG9A can be considered as a new marker of TNBC and might be considered in the future as a target to develop new specific TNBC therapies.