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在三阴性乳腺癌中过表达,其体外消除导致促癌表型的抑制。

Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of Pro-Cancer Phenotypes.

作者信息

Claude-Taupin Aurore, Fonderflick Leïla, Gauthier Thierry, Mansi Laura, Pallandre Jean-René, Borg Christophe, Perez Valérie, Monnien Franck, Algros Marie-Paule, Vigneron Marc, Adami Pascale, Delage-Mourroux Régis, Peixoto Paul, Herfs Michael, Boyer-Guittaut Michaël, Hervouet Eric

机构信息

INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University Bourgogne Franche-Comté F-25000 Besançon, France.

Department of Pathology, University Hospital of Besançon, F-25000 Besançon, France.

出版信息

Cells. 2018 Dec 6;7(12):248. doi: 10.3390/cells7120248.

DOI:10.3390/cells7120248
PMID:30563263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6316331/
Abstract

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 (, , , , and ) in breast cancer tissue, and compared their expression with healthy adjacent tissue. In our study, we observed an increase in 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 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 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.

摘要

早期检测和靶向治疗已使乳腺癌(BC)相关死亡率显著下降,然而,未来仍有重要问题需要解决。其中之一将是寻找新的三阴性乳腺癌(TNBC)治疗策略,因为目前尚无有效的方法针对这种BC亚型。由于众多研究报道了靶向自噬途径治疗或限制癌症进展的可能性,我们分析了六种自噬基因( 、 、 、 、 和 )在乳腺癌组织中的表达,并将其与相邻健康组织的表达进行比较。在我们的研究中,我们观察到乳腺癌队列中TNBC样本中 mRNA表达增加。我们还表明,在石蜡包埋组织的蛋白质水平上证实了该转录本的增加。为了证实这些体内数据,我们设计了shRNA和CRISPR/Cas9驱动的对三阴性乳腺癌细胞系MDA-MB-436中 表达的抑制,以确定其在癌症表型调控中的作用。我们发现 抑制导致体外癌症特征的抑制,这表明ATG9A可被视为TNBC的新标志物,未来可能被视为开发新的特异性TNBC疗法的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/4def09d6c17e/cells-07-00248-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/82f7f84c21e2/cells-07-00248-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/a58555b05091/cells-07-00248-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/7a19d51f7a07/cells-07-00248-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/4def09d6c17e/cells-07-00248-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/82f7f84c21e2/cells-07-00248-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/a58555b05091/cells-07-00248-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/7a19d51f7a07/cells-07-00248-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1631/6316331/4def09d6c17e/cells-07-00248-g004.jpg

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