ATG9A Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of Pro-Cancer Phenotypes

Cells

Michael Herfs¹  Marie-Paule Algros²  Franck Monnien²  Leïla Fonderflick³  Paul Peixoto³  Aurore Claude-Taupin³  Valérie Perez³  Christophe Borg³  Thierry Gauthier³  Laura Mansi³  Jean-René Pallandre³  Pascale Adami³  Michaël Boyer-Guittaut³  Régis Delage-Mourroux³  Eric Hervouet³  Marc Vigneron⁴ 

[1] Boratory of Experimental Pathology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium;Department of Pathology, University Hospital of Besançon, F-25000 Besançon, France;INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University Bourgogne Franche-Comté F-25000 Besançon, France;Team Replisome Dynamics and Cancer. UMR7242 Biotechnologie et Signalisation Cellulaire, CNRS-University Strasbourg, F-67412 Illkirch, France;

关键词: ATG9A;    autophagy;    triple negative breast cancer;    MDA-MB-436;    shRNA;    CRISPR/Cas9;   

DOI  :  10.3390/cells7120248

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown