Skip to Main content Skip to Navigation
Theses

Etude du rôle de la protéine autophagique ATG9A dans les cancers du sein

Abstract : Autophagy is an intracellular process which contributes to the maintenance of cell homeostasis. The deregulation of this complex process, which requires more than 40 ATG proteins, has been shown to be involved in tumor development. In our laboratory, we analyzed a cohort of 80 breast cancers and demonstrated that ATG9A gene expression is increased in triple negative breast cancer samples compared to adjacent healthy tissues. We then studied the role of ATG9A in the triple negative breast cancer cell line MDA-MB-436 using two extinction models created with the sh-RNA or the CRISPR-Cas9 technology. Our two extinction models presented a blockade of autophagy, due to a decrease of autophagosome degradation. We also observed a decrease of in vitro and in vivo cancer phenotypes, such as proliferation, invasion or in vivo tumor growth, of sh-ATG9A cells compared to control cells. However, we did not observe any difference of cancer phenotypes between the CRISPR-CAS9 cells and the control ones. Since we still detected the presence of the ATG9A mRNA in the CRISPR models but not in the sh-RNA models, we hypothesized that this mRNA might play a role in the maintenance of breast cancer phenotypes in these cells, either by the expression of a truncated isoform of the ATG9A protein from the mutated ATG9A mRNA obtained after the action of the CRISPR-Cas9 system, or its interaction with non-coding mRNAs. If proven, this could establish ATG9A mRNA as a potential therapeutic target in triple negative breast cancers for which no targeted therapy is currently available.
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-01801758
Contributor : Abes Star :  Contact
Submitted on : Monday, May 28, 2018 - 4:31:44 PM
Last modification on : Tuesday, October 27, 2020 - 2:34:38 PM
Long-term archiving on: : Wednesday, August 29, 2018 - 2:46:57 PM

File

these_A_CLAUDETAUPIN_Aurore_20...
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01801758, version 1

Collections

Citation

Aurore Claude-Taupin. Etude du rôle de la protéine autophagique ATG9A dans les cancers du sein. Cancer. Université Bourgogne Franche-Comté, 2017. Français. ⟨NNT : 2017UBFCE007⟩. ⟨tel-01801758⟩

Share

Metrics

Record views

150

Files downloads

1565